Fact-checked by Grok 2 weeks ago

Immunization

Immunization is the process of conferring immunity to an infectious disease by artificially stimulating the body's adaptive immune response, typically through vaccination with antigens derived from pathogens that provoke antibody production and memory cell formation without causing clinical illness.^[1]^[2] This mechanism mimics natural infection but avoids its risks, enabling the immune system to recognize and neutralize the pathogen rapidly upon future exposure.^[3] Since Edward Jenner's development of the smallpox vaccine in 1796, immunization has achieved landmark successes, including the global eradication of smallpox in 1980 through coordinated vaccination campaigns that interrupted transmission worldwide.^[4]^[5] Empirical data demonstrate that routine immunization has averted tens of millions of deaths over the past half-century, substantially reducing morbidity from diseases such as measles, polio, and diphtheria by fostering herd immunity—wherein high population-level immunity curbs outbreaks by limiting pathogen spread to susceptible individuals.^[6]^[7]^[8] Despite these gains, immunization remains contentious, with debates centering on rare but documented adverse events, such as anaphylaxis or Guillain-Barré syndrome, alongside questions of long-term efficacy and policy enforcement.^[9]^[10] Large-scale studies affirm that benefits outweigh risks for most vaccines, yet vaccine hesitancy persists, driven partly by historical incidents and amplified by selective reporting in some public health narratives, underscoring the need for transparent risk-benefit assessments grounded in causal evidence rather than institutional consensus.^[11]^[12]

Fundamentals of Immunization

Definition and Core Principles

Immunization is the process of conferring or enhancing an individual's resistance to an infectious disease through the induction of a protective immune response, typically achieved by administering vaccines containing antigens derived from pathogens.^[3] This biological intervention stimulates the adaptive immune system to recognize specific foreign antigens without causing the full-blown disease, thereby preventing or mitigating infection upon subsequent exposure.^[13] Unlike natural infection, which carries risks of severe illness or death, immunization leverages controlled antigen exposure to generate long-term immunity.^[14] At its core, immunization exploits the principles of immunological memory, where initial antigen encounter activates naive B and T lymphocytes, leading to clonal expansion, differentiation into effector cells, and formation of memory cells.^[15] Effector B cells produce pathogen-specific antibodies that neutralize invaders, while cytotoxic T cells eliminate infected cells; these responses peak during primary exposure but wane, leaving memory cells poised for amplified secondary responses characterized by faster kinetics, higher antibody titers, and broader affinity maturation.^[3] This memory underpins vaccine efficacy, with protection durations varying by pathogen and vaccine type—ranging from years for measles to shorter intervals requiring boosters for tetanus.^[13] Key principles include antigen specificity, ensuring targeted immunity without cross-reactivity to host tissues, and the balance between immunogenicity and safety, where adjuvants may enhance responses in suboptimal formulations.^[15] Immunization efficacy relies on achieving sufficient antibody thresholds or cell-mediated responses to block pathogen replication or transmission, as measured by seroconversion rates in clinical trials— for instance, over 95% for many childhood vaccines post-series completion.^[1] Factors influencing success encompass host genetics, age at administration, and pathogen variability, underscoring the need for empirical validation through randomized controlled studies rather than assumptions of universal applicability.^[3]

Active Versus Passive Immunization

Active immunization involves the introduction of an antigen, such as a vaccine or pathogen, that stimulates the recipient's immune system to produce its own antibodies and memory cells, resulting in long-term protection.^[16] This process can occur naturally through infection or artificially via vaccination, engaging both humoral and cellular immune responses.^[13] In contrast, passive immunization provides pre-formed antibodies from an external source, conferring immediate but transient protection without activating the recipient's adaptive immune system.^[15] Passive immunity arises naturally through transplacental transfer of maternal IgG antibodies to the fetus or via colostrum and breast milk containing IgA, or artificially through administration of immune globulin or antitoxins.^[16] The primary distinction lies in onset and duration: active immunization requires 1-4 weeks for antibody production and peak response, but immunity persists for years or decades due to immunological memory, often lifelong for diseases like measles.^[16] ^[13] Passive immunization delivers protection within hours, yet antibody levels wane after 3-6 months, necessitating boosters or alternative strategies for sustained defense.^[17] Artificially induced passive immunity carries risks such as allergic reactions from heterologous sera, though human-derived products minimize this.^[17] Applications of active immunization dominate routine prevention, as seen in vaccines targeting pathogens like poliovirus, where post-vaccination seroconversion rates exceed 95% in children after two doses.^[13] Passive approaches serve acute scenarios, such as post-exposure prophylaxis for rabies using human rabies immune globulin alongside vaccine, or tetanus antitoxin for wound management, providing a bridge until active responses develop.^[16] Combined strategies, like maternal vaccination during pregnancy to enhance passive transfer of antibodies against pertussis, leverage both mechanisms for neonatal protection.^[18]

Aspect	Active Immunization	Passive Immunization
Mechanism	Endogenous production of antibodies and memory cells via antigen exposure.	Exogenous antibody transfer (e.g., IgG, antitoxins).
Onset of Protection	Delayed (1-4 weeks).^[16]	Immediate (hours to days).^[16]
Duration	Long-term (years to lifetime).^[13]	Short-term (weeks to 3-6 months).^[17]
Natural Examples	Recovery from infection (e.g., chickenpox).	Maternal antibodies via placenta or breast milk.^[15]
Artificial Examples	Vaccines (e.g., measles-mumps-rubella).	Immune globulin for hepatitis A or RSV monoclonal antibodies.^[16]

Herd Immunity Dynamics

Herd immunity arises when a sufficiently large fraction of a population becomes immune to a pathogen, thereby reducing the effective reproduction number below unity and interrupting transmission chains to protect susceptible individuals.^[19] The foundational threshold for herd immunity in a homogeneously mixing population derives from the basic reproduction number R_0, defined as the average number of secondary infections produced by one infected individual in a fully susceptible population; the critical immune fraction p_c is given by p_c = 1 - 1/R_0.^[19] This formula emerges from the condition that the effective reproduction number R_e = R_0 (1 - p_c) = 1, marking the tipping point where outbreaks cease without external interventions.^[19] ![Immunization_Externality.png][float-right] For vaccine-preventable diseases, R_0 varies by pathogen transmissibility: measles has an R_0 of 12–18, yielding a p_c of approximately 92–94%; pertussis ranges from 5–17, implying 80–94%; and polio is estimated at 5–7, corresponding to 80–86%.^[20] ^[21] Achieving herd immunity via vaccination requires adjusting for vaccine efficacy VE, where the critical vaccination coverage p_v satisfies p_v = 1 - (1 - p_c)/VE, often exceeding p_c if VE < 1.^[19] For measles, with two-dose VE near 97%, coverage targets surpass 95% to account for real-world deviations.^[22] Population heterogeneity in susceptibility, contact patterns, and immunity duration complicates these dynamics, often elevating the effective threshold beyond the simple $1 - 1/R_0.^[23] Superspreading events and clustered networks can lower the threshold by concentrating immunity among high-contact individuals, but waning immunity—observed in pertussis vaccines where protection fades after 4–12 years—necessitates sustained high coverage to maintain protection.^[24] ^[19] Variable susceptibility, such as age-specific risks or pre-existing immunity, further modulates R_e, as modeled in susceptible-infected-recovered-susceptible (SIRS) frameworks where reinfection risks erode herd effects over time.^[25] Real-world dynamics underscore these principles: in the U.S., measles vaccination coverage dropped to 92.7% for the 2023–2024 kindergarten cohort, below the 95% threshold, correlating with outbreaks like the 2019 cases exceeding 1,200 amid clustered unvaccinated communities.^[22] ^[26] Conversely, sustained coverage above 95% enabled measles elimination in the Americas by 2016, though reintroduction risks persist without vigilant boosting.^[27] These patterns reflect causal drivers like compliance clustering and importation, where local herd breakdown amplifies global vulnerabilities despite high aggregate immunity.^[22]

Disease	Estimated R_0	Basic Herd Threshold ($1 - 1/R_0)	Recommended Coverage (accounting for VE)
Measles	12–18	92–94%	>95%
Pertussis	5–17	80–94%	90–95%
Polio	5–7	80–86%	80–90%

Data adapted from epidemiological models; thresholds rise with imperfect vaccines or heterogeneity.^[21] ^[20]^[19]

Historical Development

Pre-Modern and Early Practices

Practices resembling immunization predated modern vaccination by centuries, primarily through variolation, a technique involving deliberate exposure to smallpox virus material to induce a milder infection and subsequent immunity. In China, the earliest documented methods emerged during the late Ming Dynasty in the 16th or 17th century, though some accounts trace rudimentary insufflation of dried smallpox scabs into the nostrils back to the Song Dynasty around the 10th century.^[28]^[29] This approach aimed to leverage the observation that survivors of mild smallpox cases rarely contracted the severe form again, conferring protection estimated at 80-90% efficacy, albeit with a mortality risk of about 1-2% from the induced infection itself.^[30]^[31] By the 17th century, variolation had spread across Asia, the Middle East, and Africa, adapting to local contexts. In the Ottoman Empire, Circassian women performed the procedure by scratching the skin and inserting pus from smallpox lesions, a method observed and documented by European travelers in the early 18th century.^[31] Similar techniques were reported in sub-Saharan Africa, where herbalists and healers used scarification with contaminated materials, predating European contact and contributing to immunity among enslaved Africans transported to the Americas.^[32] In India, subcutaneous injection of vesicular fluid was practiced, reflecting independent regional developments rather than direct diffusion, with efficacy varying based on the virulence of the source material and the recipient's health.^[31] These methods, while empirically derived from observed survivor immunity, carried inherent dangers, including unintended outbreaks if the inoculum proved too potent, underscoring the causal link between controlled exposure and adaptive immune response without full understanding of underlying mechanisms.^[33] The transmission of variolation to Europe occurred in the early 18th century, facilitated by Lady Mary Wortley Montagu, who witnessed Ottoman practices during her stay in Constantinople from 1716 to 1718 and advocated for its adoption in Britain.^[32] By 1721, variolation gained traction in England and colonial America, with figures like Cotton Mather promoting it amid Boston's smallpox outbreak, where it reportedly reduced mortality from 14% to under 3% among inoculated individuals.^[31] Despite successes, the practice's risks—transmitting the full disease in 1-5% of cases—prompted refinements, culminating in Edward Jenner's development of vaccination in 1796.^[33] Jenner, building on folk observations of dairy workers' immunity from cowpox exposure, inoculated 8-year-old James Phipps with cowpox pus from Sarah Nelmes on May 14, 1796, followed by a smallpox challenge on July 1, which failed to produce disease, demonstrating cross-protection without variola's dangers.^[4]^[34] This marked the transition from risky empirical inoculation to a safer, heterologous viral method, laying the foundation for systematic immunization while validating the principle that prior exposure to a related pathogen could prime defenses against the target disease.^[35]

19th and Early 20th Century Breakthroughs

In the late 19th century, Louis Pasteur advanced immunization through the development of attenuated vaccines, building on empirical observations of microbial weakening to induce immunity without causing disease. His anthrax vaccine, tested publicly on June 5, 1881, at Pouilly-le-Fort, France, protected 25 sheep against Bacillus anthracis spores while control animals succumbed, demonstrating active immunization's efficacy in livestock.^[36] This method involved serial passage of the bacterium in oxygen-rich conditions to attenuate virulence, a technique grounded in causal understanding of pathogen-host interactions.^[37] Pasteur extended this approach to rabies in 1885, attenuating the virus by drying infected rabbit spinal cords over potassium hydroxide, enabling graded post-exposure prophylaxis. The first human application occurred on July 6, 1885, successfully treating 9-year-old Joseph Meister after multiple rabid dog bites, marking the initial documented use of a viral vaccine in humans.^[36] These breakthroughs shifted immunization from empirical variolation to scientifically controlled attenuation, emphasizing empirical data on dose-response and timing for immune priming.^[37] Bacterial vaccine development accelerated thereafter, with Almroth Wright introducing a heat-killed typhoid vaccine in 1896, tested on British soldiers and reducing incidence during the Boer War.^[38] Waldemar Haffkine developed a cholera vaccine in 1892 at the Pasteur Institute, deploying it in India from 1893 with field trials showing protective efficacy against Vibrio cholerae.^[39] Haffkine later produced a plague vaccine in 1897, administered to over 100,000 in Bombay amid outbreaks, correlating with lower mortality in vaccinated groups.^[39] Early 20th-century innovations included whole-cell pertussis vaccines, with initial experiments in the 1910s yielding formalized Bordetella pertussis suspensions by the 1920s for combined use.^[40] The BCG vaccine for tuberculosis, attenuated over 13 years from 1908 by Albert Calmette and Camille Guérin using bile-potato medium passages of Mycobacterium bovis, was first administered to humans in 1921.^[41] These efforts relied on verifiable reductions in disease incidence from controlled inoculations, prioritizing causal evidence over anecdotal reports.^[41]

Mid-20th Century Expansion and Eradication Efforts

The inactivated poliovirus vaccine, developed by Jonas Salk, was licensed for use in the United States on April 12, 1955, following extensive field trials involving over 1.8 million children that demonstrated 80-90% efficacy against paralytic polio.^[42]^[43] Rapid rollout ensued through national campaigns, with U.S. polio cases dropping from 35,000 in 1953 to under 6,000 by 1957, prompting similar programs worldwide and laying groundwork for global eradication initiatives.^[44] The subsequent oral poliovirus vaccine by Albert Sabin, licensed in 1961, offered easier mass administration and enhanced mucosal immunity, further accelerating incidence reductions in regions like Europe and the Americas by the mid-1960s.^[44] In 1963, John Enders and colleagues licensed the first live attenuated measles vaccine using the Edmonston-B strain, which proved highly effective in preventing clinical disease and complications like encephalitis.^[45] U.S. measles cases, exceeding 500,000 annually pre-vaccine, declined by over 97% within a decade of introduction through school-based and community immunization drives.^[45] This success spurred international adoption, with the World Health Organization (WHO) integrating measles vaccination into emerging global frameworks by the late 1960s, targeting high-burden areas in Africa and Asia.^[34] Smallpox eradication efforts intensified in the mid-1960s, with WHO launching a coordinated global campaign in 1967 after earlier bids in the 1950s faltered due to insufficient funding and surveillance.^[5] Employing ring vaccination—targeting contacts of cases with the vaccinia virus vaccine—alongside intensified case reporting, the program reduced global incidence from millions of cases yearly to isolated outbreaks by 1975.^[46] The last natural case occurred in Somalia in October 1977, culminating in WHO's 1980 declaration of eradication, the first for any human infectious disease.^[47] These advances coincided with broader institutional expansion, including WHO's 1974 establishment of the Expanded Programme on Immunization (EPI), which standardized delivery of vaccines against diphtheria, tetanus, pertussis, polio, measles, and tuberculosis to children in developing nations, immunizing over 20% of the world's infants within its first decade.^[34] National programs, bolstered by U.S. and Soviet technical aid during the Cold War, vaccinated hundreds of millions, averting an estimated 2-3 million deaths annually by the 1970s across these diseases.^[48]

Late 20th to Early 21st Century Innovations

The introduction of recombinant DNA technology marked a pivotal advance in vaccine production during the late 1980s, enabling safer manufacturing without reliance on pathogen-derived material. The first recombinant vaccine, Recombivax HB for hepatitis B, was licensed in 1986, produced by expressing the virus surface antigen in yeast cells, which eliminated risks associated with plasma-derived versions used from 1981 to 1990.^[49]^[34] This approach facilitated scalable production and reduced contamination hazards, paving the way for subsequent subunit vaccines.^[50] Conjugate vaccines emerged as a major innovation in the 1980s and 1990s, addressing the poor immunogenicity of polysaccharide antigens in infants by covalently linking them to carrier proteins, thereby eliciting T-cell dependent responses and longer-lasting immunity. The Haemophilus influenzae type b (Hib) conjugate vaccine, first licensed as PRP-D in 1987, dramatically reduced invasive Hib disease incidence by over 99% in vaccinated populations within a decade of widespread use.^[49]^[51] This technology extended to pneumococcal disease with the 7-valent conjugate vaccine (PCV7, Prevnar) licensed in 2000, which targeted seven serotypes responsible for most invasive cases in children, leading to a 75-90% decline in vaccine-type pneumococcal disease shortly after implementation.^[49]^[52] Acellular pertussis vaccines replaced whole-cell formulations in combination shots (DTaP) starting in the early 1990s, incorporating purified toxins and adhesins to minimize reactogenicity while maintaining efficacy against severe pertussis; the first U.S. DTaP licenses occurred between 1991 and 1997.^[51]^[53] Live-attenuated vaccines also advanced, exemplified by the varicella vaccine licensed in 1995, which reduced chickenpox incidence by over 90% in two-dose regimens and curtailed complications like shingles in later life.^[49]^[54] In the early 2000s, virus-like particle (VLP) technology underpinned prophylactic vaccines against viruses lacking prior immunization options. The human papillomavirus (HPV) vaccine Gardasil, approved in 2006, targeted oncogenic types 16 and 18 (70% of cervical cancers) plus wart-causing types 6 and 11, demonstrating near-complete prevention of vaccine-type infections and precancerous lesions in clinical trials involving over 20,000 participants.^[49]^[55] Oral rotavirus vaccines, reintroduced as RotaTeq in 2006 after an earlier version's withdrawal, used reassortant strains to avert severe gastroenteritis, reducing hospitalizations by 85-98% in post-licensure studies.^[51]^[34] These innovations collectively expanded coverage to mucosal pathogens and cancers, leveraging genetic engineering for precision antigen design.^[56]

Types and Technologies

Traditional Inactivated and Live-Attenuated Vaccines

Inactivated vaccines contain pathogens, typically viruses or bacteria, that have been killed or rendered non-infectious through chemical (e.g., formalin) or physical (e.g., heat) inactivation processes, preventing replication while preserving antigenic structures to stimulate an immune response.^[57]^[58] These vaccines primarily elicit humoral immunity via antibody production but generate comparatively weaker cellular T-cell responses compared to natural infection, often necessitating multiple doses or boosters for sustained protection.^[59] The approach dates to the late 19th century, with the first inactivated vaccines developed against typhoid and cholera bacteria in 1896 using heat-killed organisms.^[60] Pioneered prominently by Jonas Salk in 1955, the inactivated polio vaccine (IPV) marked a milestone, demonstrating 60-90% efficacy against paralytic poliomyelitis after two doses and over 90% after three in field trials involving over 1.8 million children.^[61] Other examples include seasonal influenza vaccines, which undergo annual strain updates and show 40-60% effectiveness against influenza-like illness in randomized trials, hepatitis A vaccine (95% seroprotection after two doses), and rabies vaccine (near 100% efficacy post-exposure with proper regimen).^[62] Inactivated vaccines cannot cause the target disease due to the absence of viable pathogens, rendering them suitable for immunocompromised individuals, though adjuvants like aluminum salts are often added to enhance immunogenicity.^[63] Common adverse events are mild, such as local injection-site reactions, with rare systemic effects like allergic responses occurring in fewer than 1 in 100,000 doses across surveillance data.^[64] Live-attenuated vaccines employ weakened strains of live pathogens, propagated through serial passage in cell cultures or animal models to reduce virulence while retaining replicative capacity, thereby mimicking natural infection to induce robust, multifaceted immunity.^[65] This replication in the host triggers both strong antibody responses and cellular immunity, including cytotoxic T cells, often conferring long-term protection with fewer doses—typically one or two—due to the pathogen's ability to disseminate antigens endogenously.^[66]^[67] Historical development includes Louis Pasteur's 1885 rabies vaccine, attenuated via desiccation and nerve tissue propagation, and Albert Sabin's oral polio vaccine (OPV) in 1961, which achieved over 95% efficacy against poliomyelitis in mass campaigns.^[49] Key examples encompass the measles-mumps-rubella (MMR) vaccine, licensed in 1971, with two doses yielding 97% efficacy against measles and 88% against mumps based on clinical data; varicella vaccine (1995), preventing 90% of moderate/severe chickenpox cases; and rotavirus vaccines like RotaTeq (2006), reducing severe gastroenteritis hospitalizations by 85-98% in infants.^[68]^[66] These vaccines excel in herd immunity thresholds, as seen with smallpox eradication via Edward Jenner's cowpox-based vaccine (1796), which induced cross-protective immunity leading to global elimination by 1980.^[34] However, contraindications apply to immunocompromised hosts due to risks of uncontrolled replication; rare complications include vaccine-associated paralytic poliomyelitis from OPV (1 in 2.4 million doses) and potential reversion to virulence in strains like yellow fever vaccine.^[69]^[70] Overall, live-attenuated platforms demonstrate superior duration of immunity in healthy populations but require cold-chain logistics for viability.^[71] Compared to inactivated counterparts, live-attenuated vaccines generally offer higher efficacy and broader immune activation at lower doses but carry theoretical risks of transmission or mutation, necessitating rigorous attenuation validation through animal models and genetic stability assessments.^[72] Both types form the backbone of routine immunization schedules, underpinning reductions in diseases like polio (99% global case drop since 1988) through combined strategies.^[29]

Subunit, Toxoid, and Conjugate Vaccines

Subunit vaccines contain specific antigenic fragments, such as viral proteins or bacterial polysaccharides, purified or recombinantly produced to induce targeted immune responses without incorporating whole pathogens or replication-competent material.^[13] This approach minimizes risks associated with live or inactivated vaccines while focusing the immune system on key epitopes for antibody production and cellular immunity.^[73] The hepatitis B surface antigen vaccine, the first recombinant subunit vaccine, was licensed in 1986 using yeast-expressed viral proteins that self-assemble into virus-like particles, achieving seroprotection rates exceeding 95% in healthy adults after three doses.^[74] Modern examples include protein subunit formulations for SARS-CoV-2, where injected spike proteins are processed by antigen-presenting cells to generate neutralizing antibodies.^[75] Toxoid vaccines utilize formalin-inactivated exotoxins from bacteria, rendering them non-toxic while preserving immunogenicity to elicit neutralizing antibodies against the pathogen's harmful effects.^[76] Tetanus toxoid, developed in 1924, was widely deployed during World War II, reducing tetanus mortality among wounded soldiers by over 95% compared to unvaccinated cohorts.^[77] Diphtheria toxoid, introduced in the early 1920s, similarly detoxifies the bacterial toxin while maintaining its receptor-binding domain, forming the core of combination vaccines like DTaP that provide durable protection with booster doses every 10 years.^[78] These vaccines do not prevent bacterial colonization but block toxin-mediated damage, necessitating adjunct tetanus immune globulin for wound management in underimmunized individuals.^[79] Conjugate vaccines covalently link purified bacterial capsular polysaccharides—typically T-cell-independent antigens that elicit weak, short-lived IgM responses in infants—to immunogenic carrier proteins like diphtheria or tetanus toxoids, shifting the response to T-cell-dependent pathways for enhanced IgG production, affinity maturation, and immunological memory.^[80] The first such vaccine, against Haemophilus influenzae type b (Hib), was licensed in 1987 and demonstrated efficacy greater than 95% against invasive disease in clinical trials, leading to near-elimination of Hib meningitis in vaccinated populations.^[81] Pneumococcal conjugate vaccines (PCVs), such as PCV13 approved in 2010, target multiple serotypes and have reduced invasive pneumococcal disease by 70-90% in children under 5 years, though serotype replacement by non-vaccine strains has prompted expansions like PCV20.^[82] Meningococcal conjugates similarly protect against serogroups A, C, W, and Y, with post-licensure data showing 80-90% effectiveness against vaccine-type invasive disease.^[83]

Emerging Platforms Including mRNA and Viral Vectors

Messenger RNA (mRNA) vaccines represent a novel platform where synthetic mRNA encoding a target antigen is delivered into host cells, directing transient production of the antigen to stimulate both humoral and cellular immune responses without altering the host genome.^[84] This technology leverages lipid nanoparticles for mRNA protection and cellular uptake, addressing historical challenges like instability and innate immune activation through chemical modifications such as nucleoside replacements.^[85] Development traces back to mRNA discovery in the 1960s and key experiments in the 1980s and 1990s, but practical vaccines emerged prominently during the COVID-19 pandemic, with the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 receiving emergency use authorizations in December 2020 after phase 3 trials demonstrating 95% and 94.1% efficacy against symptomatic infection, respectively.^[86] ^[87] Beyond SARS-CoV-2, mRNA platforms are under investigation for influenza, Zika, and cancer, offering advantages in rapid sequence-based design and scalable in vitro transcription manufacturing, potentially enabling responses to emerging pathogens within months.^[88] However, limitations include cold-chain requirements for stability and observed rare adverse events like myocarditis, occurring at rates of approximately 1-10 per 100,000 doses primarily in young males post-second dose.^[89] ^[90] Viral vector vaccines utilize replication-incompetent viruses, such as adenoviruses or vesicular stomatitis virus, engineered to express foreign antigens by inserting genetic material into the vector genome, prompting antigen presentation via infected host cells and eliciting robust T-cell and antibody responses that mimic natural infection.^[91] Non-replicating vectors avoid uncontrolled spread while preserving immunogenicity, with examples including the adenovirus-based AstraZeneca-Oxford AZD1222 (70-90% efficacy against symptomatic COVID-19 in 2020 trials) and the single-dose Johnson & Johnson Ad26.COV2.S (66-85% efficacy), both authorized in early 2021.^[92] ^[93] The rVSV-ZEBOV vaccine, approved in 2019 for Ebola, demonstrated 97.5% efficacy in a 2015 ring vaccination trial, highlighting the platform's utility for hemorrhagic fevers.^[94] Advantages encompass strong cellular immunity and thermostability compared to mRNA, facilitating easier logistics in low-resource settings, though pre-existing immunity to common vectors like adenovirus type 5 can reduce efficacy, necessitating rare serotype selection or prime-boost regimens.^[95] Safety profiles show rare thrombotic events with some adenovirus vectors (e.g., 1 in 100,000 for AZD1222), lower than mRNA-associated myocarditis risks in certain demographics.^[89] ^[96] Comparative analyses of COVID-19 vaccines indicate mRNA platforms initially outperformed viral vectors in preventing symptomatic disease (e.g., 94-95% vs. 62-90%), but both reduced severe outcomes by over 90%, with waning efficacy against infection prompting boosters.^[93] ^[96] Emerging hybrid strategies and self-amplifying mRNA variants aim to enhance durability and breadth, while viral vectors explore chimeric designs to evade immunity; ongoing trials as of 2025 target multivalent formulations for respiratory viruses.^[97] These platforms' speed—evident in sub-one-year COVID vaccine timelines—contrasts traditional methods requiring pathogen cultivation, though long-term immunogenicity and variant escape remain under scrutiny via systems like VAERS and global surveillance.^[98]^[99]

Efficacy Evaluation

Clinical Trial Methodologies and Results

Vaccine clinical trials follow a phased approach to evaluate safety, immunogenicity, and efficacy prior to regulatory approval. Phase I trials involve small cohorts of 20-100 healthy volunteers to assess initial safety, dosage, and immune response profiles, often without placebo controls due to ethical constraints on withholding potential protection.^[100] Phase II expands to 100-300 participants representative of the target population, focusing on optimal dosing, immunogenicity (e.g., antibody titers), and preliminary efficacy signals while monitoring adverse events.^[101] Phase III constitutes large-scale, randomized, double-blind, placebo-controlled trials with thousands of participants to measure efficacy against predefined endpoints such as infection rates or disease incidence, alongside comprehensive safety data; these trials emphasize statistical power to detect differences in event rates between vaccinated and control groups.^[102] Post-approval Phase IV surveillance monitors long-term effects in broader populations.^[100] Methodologies prioritize randomized allocation to minimize bias, with endpoints tailored to the pathogen—virological confirmation for infection prevention or clinical outcomes like paralysis for polio—and often include stratified sampling by age, risk factors, or comorbidities.^[103] Efficacy is typically reported as relative risk reduction, calculated from hazard ratios or attack rates in intention-to-treat analyses, though absolute risk reductions vary by baseline disease incidence.^[104] Challenges include ethical barriers to placebo use in endemic settings, leading to historical observed-control designs, and the need for surrogate markers like seroconversion when disease rarity precludes direct measurement.^[105] The 1954 Salk inactivated polio vaccine field trial exemplified early large-scale methodology, randomizing over 1.8 million U.S. children into vaccinated (about 650,000), placebo (about 750,000), and observed (no injection) arms, yielding 80-90% efficacy against paralytic poliomyelitis based on observed case reductions.^[106] Cases in vaccinated second-graders dropped to 16 per 100,000 versus 57 per 100,000 in placebo recipients, with statistical significance confirmed via log-rank tests on incidence data.^[107] Live-attenuated measles vaccines in 1960s cooperative field trials demonstrated 95% or higher efficacy against clinical measles after one year, with combined schedules maintaining protection above 95% through serological correlates and attack rate comparisons in exposed cohorts.^[108] HPV prophylactic vaccines, such as quadrivalent Gardasil, showed over 90% efficacy against vaccine-type persistent infections and precancerous lesions in Phase III trials involving thousands of women, with immunogenicity bridging to younger ages via non-inferior antibody responses.^[109] mRNA COVID-19 vaccines in 2020 Phase III trials reported 94-95% efficacy against symptomatic SARS-CoV-2 infection in initial strains, derived from blinded, placebo-controlled studies with over 30,000 participants each; Pfizer-BioNTech's trial recorded 162 cases in placebo versus 8 in vaccinated arms, while Moderna's showed 185 versus 11, using PCR-confirmed endpoints within two months post-second dose. These results, however, reflected relative efficacy in low-prevalence settings, with absolute reductions under 1% given baseline risks below 2%.^[110]

Real-World Effectiveness Data

Real-world vaccine effectiveness (VE) is assessed through observational studies, surveillance systems, and population-level data, capturing performance under routine conditions including variable adherence, circulating strains, and comorbidities, unlike controlled clinical trials.^[111] These metrics often measure reductions in infection, symptomatic disease, hospitalization, or mortality attributable to vaccination. For measles, two doses of measles-mumps-rubella (MMR) vaccine exhibit VE of 93-97% against clinical disease in outbreak settings across diverse populations.^[112]^[113] Population-scale analyses indicate MMR vaccination averted nearly 94 million deaths globally from 1974 to 2024, with incidence dropping over 99% in high-coverage regions.^[7] Breakthrough cases occur rarely, primarily in those with only one dose or waning immunity over decades, though protection against severe outcomes remains robust.^[114] Polio vaccines have achieved near-eradication of wild poliovirus types 2 and 3, with global paralytic cases reduced by over 99.9% since 1988 through oral and inactivated formulations in mass campaigns.^[115]^[116] In endemic areas like Afghanistan and Pakistan, high-coverage oral polio vaccine (OPV) interrupted transmission chains, though vaccine-derived strains emerge in under-immunized pockets, necessitating surveillance and targeted boosts.^[117] Human papillomavirus (HPV) vaccines demonstrate VE exceeding 90% against vaccine-targeted cervical precancers and cancers in real-world cohorts vaccinated before exposure.^[118] Swedish registry data from 2006-2020 showed zero invasive cervical cancers among girls vaccinated at ages 12-13, versus expected rates in unvaccinated peers, with 87% reduction in women up to age 30.^[119]^[120] In contrast, acellular pertussis vaccines show initial VE of 80-90% post-series but wane to 40-70% within 2-5 years, correlating with adolescent and adult epidemics despite coverage over 90% in the U.S. and Europe.^[121]^[122] Observational studies attribute resurgences to shorter duration of immunity compared to whole-cell predecessors, with boosters providing temporary restoration but not preventing transmission shifts.^[123]^[124] Seasonal influenza vaccines yield pooled VE of 40-50% against laboratory-confirmed infection in meta-analyses of test-negative designs, varying by age, strain match, and prior vaccination history.^[125] Children under 18 average 49% VE, adults 37%, with higher protection against hospitalization (50-60%) in older groups, though effectiveness declines post-mismatch seasons or repeated dosing without antigenic update.^[126]^[127]

Factors Influencing Vaccine Performance

Vaccine performance, encompassing both efficacy in controlled trials and effectiveness in population settings, varies due to interactions among host characteristics, pathogen biology, vaccine properties, and external conditions. Host factors such as age profoundly affect immune responses; immunosenescence in older adults diminishes antibody production and T-cell function, leading to reduced prophylactic efficacy for vaccines like influenza and shingles, where seroconversion rates decline progressively with age.^[128]^[129] Similarly, immunocompromised individuals, including those with HIV or undergoing chemotherapy, exhibit weaker humoral and cellular responses due to impaired innate and adaptive immunity, resulting in lower protection against targeted pathogens.^[130]^[131] Genetic variations in host immune-related genes further modulate outcomes, with polymorphisms influencing cytokine production or antigen presentation and thereby altering vaccine-induced immunogenicity across populations.^[131]^[132] Pathogen evolution poses a persistent challenge, as antigenic drift or shift in viruses like influenza enables immune escape, eroding vaccine matching and effectiveness; for instance, mismatches between vaccine strains and circulating variants have historically reduced seasonal influenza vaccine efficacy by 10-20% in some seasons.^[133]^[134] In bacteria, selective pressure from vaccination can drive virulence evolution or resistance, though this is less common in sterilizing immunity vaccines; examples include pertussis toxin mutations diminishing acellular vaccine protection over time.^[135] Pre-existing immunity from prior infections or vaccinations also interacts with new doses, sometimes via original antigenic sin, where responses favor older epitopes and weaken against evolved strains, as observed in repeated influenza immunizations.^[136] Vaccine-specific attributes, including formulation and dosing, impact performance; live-attenuated vaccines generally elicit stronger, longer-lasting immunity than inactivated ones but require intact host immunity, while adjuvants enhance responses in low-responders like the elderly.^[137] Improper storage disrupts molecular stability, with temperatures outside 2-8°C causing potency loss—freezing aluminum-adjuvanted vaccines irreversibly aggregates antigens, and heat exposure denatures proteins, as evidenced by reduced immunogenicity in field studies of heat-stressed lots.^[138]^[139] Cold chain failures, prevalent in low-resource settings, contribute to up to 20% of vaccine wastage globally, directly correlating with diminished real-world effectiveness.^[140] Population-level factors, such as adherence to multi-dose schedules and exposure risks, further modulate outcomes; incomplete series halve protection for vaccines like hepatitis B, while high variant circulation amplifies breakthrough infections in partially immune groups.^[141] Co-morbidities like obesity or diabetes exacerbate poor responses via chronic inflammation, underscoring the need for tailored strategies to optimize performance across diverse cohorts.^[142]^[130]

Safety and Adverse Events

Common and Mild Reactions

Local reactions at the injection site, including pain, erythema, and swelling, represent the most prevalent mild adverse events following immunization, typically resolving within 1-3 days. These occur in 20-40% of recipients for diphtheria-tetanus-pertussis (DTP/DTaP) vaccines and 10-25% for inactivated polio vaccine (IPV).^[143] For hepatitis B vaccine, injection site pain affects 3-29% of doses.^[143] Such responses arise from immune cell recruitment and are more pronounced with adjuvanted formulations, but they do not indicate vaccine failure or systemic harm.^[144] Systemic mild reactions, such as low-grade fever and fatigue, are also commonplace, signaling cytokine-mediated immune activation. After DTP/DTaP administration, fever arises in about 25% of cases, while irritability affects up to 50%, predominantly in young children.^[143] Influenza vaccines elicit systemic symptoms like myalgia and fatigue in 10-40% of recipients.^[143] For Haemophilus influenzae type b (Hib) vaccines, fever occurs in 5-10%.^[143] These events peak within 24-48 hours post-vaccination and rarely require medical attention beyond symptomatic relief like antipyretics.^[145] Live attenuated vaccines, such as measles-mumps-rubella (MMR), produce delayed mild reactions mimicking subclinical infection, including fever and transient rash in 5-15% of children, usually 7-12 days after dosing.^[143] Local reactions here are milder, at 5-15%.^[143] Oral polio vaccine (OPV) rarely causes notable mild effects (1-5% systemic), reflecting its non-invasive route.^[143] Across routine schedules, mild events constitute the majority of post-vaccination reports in surveillance systems, with rates influenced by factors like dose number and recipient age—higher in infants for irritability and lower in adults for fever.^[146] Empirical data from clinical trials and pharmacovigilance affirm these as expected, self-limiting outcomes of adaptive immunity, far outweighed by protection against target diseases.^[147]

Rare Serious Events and Reporting Systems

Rare serious adverse events following immunization, though infrequent, include anaphylaxis, with an estimated incidence of 1.3 cases per million doses administered across multiple vaccine types in large-scale studies.^[148] Guillain-Barré syndrome (GBS) has shown temporal associations with specific vaccines, such as certain influenza formulations historically and adenovirus-vectored COVID-19 vaccines, where reporting odds ratios indicate elevated signals but absolute rates remain low at approximately 1-3 cases per million doses, often comparable to or slightly above background population incidence of 1-2 per 100,000 annually.^[149] ^[150] Other documented rare events encompass intussusception linked to rotavirus vaccines (about 1-5 excess cases per 100,000 infants) and vaccine-associated paralytic poliomyelitis from live oral polio vaccine (1 in 2.4 million doses), events that prompted formulation changes or withdrawals when risks exceeded benefits in specific contexts.^[151] These occurrences highlight the need for ongoing surveillance, as most vaccines demonstrate no causal link to serious events beyond exceedingly rare hypersensitivity or immune-mediated responses, with benefits in disease prevention far outweighing risks based on epidemiological data.^[152] The Vaccine Adverse Event Reporting System (VAERS), established in 1990 and operated jointly by the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA), functions as a passive surveillance tool accepting voluntary reports of adverse events from healthcare providers, vaccine manufacturers, and the public to detect potential safety signals.^[153] Serious events, defined as those resulting in death, hospitalization, or permanent disability, comprised about 14% of VAERS reports from 1991-2001, though the system captures only a fraction of occurrences due to underreporting and includes unverified data without establishing causality.^[154] ^[155] Limitations include reliance on self-reported information, potential for reporting biases (e.g., heightened submissions during media scrutiny), and inability to calculate incidence rates directly, necessitating follow-up through active systems like the Vaccine Safety Datalink (VSD) for verification.^[156] ^[157] Internationally, the World Health Organization (WHO) supports pharmacovigilance via the Global Vaccine Safety Initiative (GVSI) and collaborations with the Uppsala Monitoring Centre, aiding countries in establishing national systems for signal detection and response, with progress tracked through indicators like adverse event reporting rates per 100,000 population.^[158] ^[159] These frameworks emphasize integrating passive and active methods to address gaps in low-resource settings, where underreporting can exceed 90%, while prioritizing causality assessments through cohort studies or case-control analyses rather than raw reports alone.^[160] Despite advancements, global systems share VAERS-like constraints, underscoring the importance of triangulating data sources to distinguish vaccine-attributable risks from coincidental events.^[161]

Long-Term Monitoring and Causality Assessment

Long-term monitoring of vaccine safety relies on both passive and active surveillance systems to detect potential adverse events occurring months or years post-vaccination. In the United States, the Vaccine Adverse Event Reporting System (VAERS), co-managed by the CDC and FDA, serves as a passive system where healthcare providers, vaccine manufacturers, and the public report suspected adverse events, enabling early signal detection for rare or delayed effects.^[162] Complementing this, the Vaccine Safety Datalink (VSD), a collaboration between the CDC and multiple healthcare organizations covering over 9 million individuals, facilitates active surveillance through electronic health records, allowing for cohort studies and rate comparisons to assess long-term risks such as autoimmune disorders or neurological conditions.^[163] Internationally, similar systems like the WHO's global AEFI (adverse event following immunization) monitoring integrate data from national programs to track patterns over extended periods.^[164] Causality assessment for reported events employs structured methodologies to distinguish temporal associations from true causal links, often using criteria akin to the Bradford Hill guidelines adapted for vaccines, which evaluate strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy.^[165] The WHO-UMC causality assessment algorithm classifies events into categories such as "consistent with causal association," "indeterminate," "inconsistent," or "undclassified," based on prior evidence, dechallenge/rechallenge data (where feasible), and exclusion of alternative causes; this tool has been applied to over 97% of VAERS reports, with most deemed unrelated or unlikely related.^[166]^[167] For long-term events, assessments incorporate epidemiological data, such as observed-versus-expected ratios from large cohorts, to account for background incidence rates and confounders like age, comorbidities, or concurrent exposures.^[168] Peer-reviewed longitudinal studies exemplify these processes, often finding no elevated risks for chronic conditions attributable to vaccines. A Danish cohort study of over 650,000 children exposed to aluminum-adjuvanted vaccines showed no increased incidence of autoimmune, neurodevelopmental, or allergic disorders over 10+ years compared to unexposed peers.^[169] Similarly, analyses of routine childhood immunizations in birth cohorts have not identified causal links to long-term neuropsychological outcomes, with hazard ratios near 1.0 after adjusting for familial and environmental factors.^[170] However, challenges persist: underreporting in passive systems like VAERS (estimated at 1-10% capture rate for serious events) and selection biases in active databases can obscure rare signals, while establishing causality for delayed events requires large-scale, multi-decade follow-up to disentangle from natural disease progression.^[171] In cases like myocarditis post-mRNA vaccination, causality has been affirmed through temporal clustering, dose-response patterns, and mechanistic evidence from biopsies, prompting updated monitoring protocols.^[172] Ongoing refinements emphasize integrating genomic data and advanced analytics, such as machine learning for signal detection in VSD, to enhance causality inference amid evolving vaccine schedules and populations.^[173] Despite robust evidence from millions of person-years of observation indicating overall safety, absolute rarity of long-term effects necessitates perpetual vigilance, as historical precedents like the 1976 swine flu vaccine's Guillain-Barré syndrome association demonstrate the value of sustained assessment.^[174]

Controversies and Skepticism

Persistent Claims on Autism and Neurodevelopmental Disorders

Persistent claims linking immunization to autism spectrum disorder (ASD) and other neurodevelopmental disorders originated primarily from a 1998 case series published in The Lancet by Andrew Wakefield and colleagues, which proposed a connection between the measles-mumps-rubella (MMR) vaccine, gastrointestinal issues, and regressive autism in 12 children.^[175] The study was retracted in 2010 after investigations revealed ethical violations, data manipulation, and undisclosed financial conflicts, including Wakefield's funding from lawyers suing vaccine manufacturers; he was subsequently stripped of his medical license.^[176] Despite this, the paper fueled public concern, contributing to MMR vaccine hesitancy and measles outbreaks, such as the 2008 U.S. cases linked to unvaccinated communities.^[177] Subsequent hypotheses shifted from MMR to thimerosal, a mercury-containing preservative in some vaccines, posited to cause neurotoxicity akin to ASD symptoms, and later to the overall vaccine schedule overloading immune systems in vulnerable children.^[178] Proponents, including groups like Children's Health Defense, cite temporal correlations—ASD diagnoses often emerge around 12-18 months, coinciding with vaccination timing—and anecdotal reports of regression post-vaccination, arguing that large-scale studies overlook subgroup risks or underreport via systems like VAERS.^[179] These claims persist amid rising ASD prevalence, from 1 in 150 U.S. children in 2000 to 1 in 36 in 2020 per CDC data, though diagnostic expansions and awareness explain much of the increase rather than incidence changes.^[180] Epidemiological evidence consistently refutes causal links. A 2019 Danish cohort study of 657,461 children born 1999-2010 found no increased ASD risk among MMR-vaccinated versus unvaccinated children (adjusted hazard ratio 0.93; 95% CI, 0.85-1.02), with similar null results for autism with regression.^[181] Meta-analyses of over 1.2 million children across multiple countries confirm no association between MMR, thimerosal, or mercury exposure and ASD or other neurodevelopmental outcomes.^[182] The U.S. Institute of Medicine's 2004 review of 14 large studies rejected biological mechanisms for MMR-autism links, citing lack of evidence for persistent measles virus or immune dysregulation from vaccination.^[183] Thimerosal removal from most U.S. childhood vaccines by 2001 provided a natural experiment; California ASD cases continued rising from 1999-2007, with prevalence increasing 7-fold in some cohorts despite ethylmercury elimination, undermining toxicity claims.^[184]^[185] CDC analyses of Vaccine Safety Datalink data from millions of children show no differences in neurodevelopmental disorders between thimerosal-exposed and unexposed groups.^[186] Critics of these findings, often from advocacy sources, highlight potential confounders like genetic factors or aluminum adjuvants, but no peer-reviewed studies demonstrate causality, and hypothesis-testing trials (e.g., 2005 Jamaican thimerosal study) yield null results.^[187] While institutional sources like CDC and WHO affirm vaccine safety based on this data—issuing 2025 statements reiterating no ASD links—skeptics question their independence due to industry funding ties, though independent international cohorts replicate findings.^[188]^[180] Ongoing research into ASD etiology emphasizes genetics (heritability ~80%) and prenatal factors over postnatal vaccination, with no verified causal pathway identified despite decades of scrutiny.^[189] Claims endure partly from confirmation bias and media amplification of outliers, yet empirical rejection of vaccine-ASD hypotheses supports immunization's net benefits in preventing infectious diseases that themselves risk neurodevelopmental harm, such as measles encephalitis.^[178]

Concerns Over Vaccine Schedules and Immune Overload

Some parents and advocacy groups have expressed concerns that the expanded childhood immunization schedules, which now recommend multiple vaccines administered simultaneously or in close succession during infancy, may overburden the developing immune system, potentially leading to increased susceptibility to non-target infections, autoimmune conditions, or general immune dysregulation.^[190] This hypothesis posits that the cumulative antigenic load from vaccines exceeds the infant's capacity to mount specific responses without compromising overall immune function, a view held by approximately 23-25% of parents in U.S. surveys conducted around 2000.^[190] Critics, including certain pediatricians advocating delayed schedules, argue that natural environmental exposures historically spaced antigens differently, and rapid vaccine introduction could mimic "antigenic overload" akin to observations in animal models under extreme challenge, though human data supporting this remains limited.^[191] Childhood vaccine schedules have expanded significantly since the mid-20th century; in the early 1950s, only four vaccines were routinely available (diphtheria, tetanus, pertussis, and smallpox), often combined into fewer doses, whereas by 2015, U.S. children could receive up to 24 immunizations by age two, encompassing vaccines for hepatitis B, rotavirus, Haemophilus influenzae type b, pneumococcal disease, and others, with peak dosing at visits like 2, 4, and 6 months involving 3-5 injections.^[192] This increase reflects advancements in vaccine technology, such as acellular pertussis and conjugate polysaccharides, which reduced total antigens per dose—modern schedules expose children to fewer antigens overall than 1990s equivalents despite more vaccines—yet concerns persist over the timing and volume in early infancy when the immune system relies more on innate responses and maternal antibodies.^[193] Peer-reviewed analyses, including a 2002 Institute of Medicine review and subsequent studies, have consistently found no evidence that multiple simultaneous vaccines weaken or overload the infant immune system.^[190] Infants encounter an estimated 2,000-6,000 unique antigens daily from bacteria, food, and environmental microbes via mucosal surfaces, far exceeding the 100-200 antigens in a full vaccine schedule, enabling robust responses without depletion of immune resources.^[194] A 2018 nested case-control study of over 650,000 children linked electronic health records and found no association between cumulative vaccine antigen exposure in the first 23 months and increased risk of non-vaccine-targeted infections, autism spectrum disorder, or other developmental issues, even among high-exposure cohorts.^[193] Similarly, the World Health Organization's Global Advisory Committee on Vaccine Safety concluded in 2002, reaffirmed in 2006, that available epidemiological data do not support immune overload, as vaccinated children exhibit comparable or superior protection against target diseases without heightened vulnerability to others.^[195] While short-term reactogenicity, such as fever or local reactions, may increase slightly with multiple injections—observed in cohort studies from 1991-2000 showing odds ratios of 1.2-2.0 for medically attended fever post-combination visits—no causal link to long-term immune compromise has been established.^[196] Randomized trials of combination vaccines (e.g., DTaP-IPV-Hib-HepB) demonstrate equivalent immunogenicity and safety profiles to separate administration, with protective antibody levels achieved in over 95% of recipients.^[197] Critics' claims often rely on theoretical models or selective adverse event reports rather than controlled comparisons, and bodies like the CDC affirm that simultaneous vaccination aligns with the immune system's proven capacity, as evidenced by decades of post-licensure surveillance showing no population-level immune deficits.^[198] Ongoing research, such as infant response profiling at routine vaccination ages, continues to affirm developmental resilience without overload signals.^[199] Informed consent requires that individuals receive comprehensive information about potential benefits, risks, and alternatives to a medical intervention, and that their agreement be voluntary, free from coercion. This principle, rooted in post-World War II ethical frameworks like the Nuremberg Code, mandates voluntary participation without undue influence, particularly for experimental procedures, though it has been extended to routine medical care in many jurisdictions.^[200] ^[201] In vaccination contexts, however, the absence of standardized consent processes in the United States—varying by state and often limited to brief discussions—raises concerns about whether true comprehension and voluntariness are achieved, especially for pediatric immunizations where parental proxy consent applies.^[202] Vaccine mandates, such as those for school entry or employment, introduce ethical tensions by prioritizing collective public health benefits like herd immunity over individual bodily autonomy. The 1905 U.S. Supreme Court case Jacobson v. Massachusetts established that states could enforce smallpox vaccination with fines or quarantine for refusal during outbreaks, provided the measures bore a "real or substantial relation" to public safety, but it allowed limited exemptions and did not authorize forced administration.^[203] Proponents of mandates argue from utilitarian grounds that high vaccination coverage prevents outbreaks and protects vulnerable populations unable to vaccinate, citing data where non-medical exemptions correlate with 1.5-2.3% drops in coverage for diseases like MMR and DTaP, alongside increased measles clusters in high-exemption areas.^[204] ^[205] Critics, emphasizing deontological rights to self-ownership, contend that coercion—such as job loss or educational exclusion—undermines consent's voluntariness, potentially eroding trust in health systems and leading to lower overall uptake if perceived as authoritarian.^[206] ^[207] Exemptions mitigate some autonomy concerns but highlight mandate limitations: all U.S. states permit medical exemptions, while 47 allow religious ones, and 15 philosophical, yet rising non-medical exemption rates—reaching 3.6% among kindergartners in 2024-2025—have coincided with coverage below 93% for key vaccines, facilitating localized outbreaks.^[208] ^[209] During the COVID-19 pandemic, mandates for healthcare workers and others sparked debates, with peer-reviewed analyses concluding they could be ethically defensible if less restrictive measures (e.g., incentives) fail and efficacy data supports reduced transmission, but only after exhausting autonomy-respecting alternatives to avoid disproportionate harm to personal liberties.^[210] ^[211] Empirical reviews indicate such policies boosted short-term compliance but risked backlash, including workforce shortages in mandate-heavy sectors, underscoring the need for transparent risk-benefit communication to preserve consent integrity.^[212]^[213]

Industry Influence and Data Transparency

The pharmaceutical industry exerts significant influence on vaccine regulation through financial mechanisms, including user fees that constitute approximately 45% of the U.S. Food and Drug Administration's (FDA) overall budget and up to 65% of funding for human drug regulatory activities, potentially compromising agency independence by tying resources to industry submissions.^[214]^[215] These Prescription Drug User Fee Act (PDUFA) collections, enacted in 1992 and periodically reauthorized, expedite review processes but have raised concerns about regulatory capture, as FDA priorities may align more closely with fee-paying sponsors than public interest.^[216] Similarly, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) manages conflicts of interest through disclosures and recusal policies, with reported financial ties among members dropping to historic lows in recent years—fewer than 5% of advisors disclosing relevant conflicts in the past decade—yet structural dependencies on industry-funded data persist.^[217]^[218] Lobbying further amplifies industry sway, with the pharmaceuticals and health products sector spending over $4.7 billion on U.S. federal lobbying from 1999 to 2018, including targeted efforts on vaccination policies such as school mandates and liability protections.^[219] In state-level policymaking, vaccine manufacturers like Merck have been criticized for aggressive, nontransparent lobbying tactics, such as undisclosed meetings with legislators to promote mandates for products like the HPV vaccine, blurring lines between acceptable advocacy and undue pressure.^[220] Recent escalations include record lobbying expenditures during the COVID-19 pandemic, exceeding $250 million in early 2020 alone by major firms, often focused on securing emergency authorizations, patent extensions, and global distribution frameworks that prioritize proprietary interests.^[221]^[222] Data transparency in vaccine clinical trials remains limited, hindering independent verification and contributing to skepticism; for instance, individual participant data from major COVID-19 vaccine trials were not publicly available for months or years post-approval, restricting post-hoc analyses of efficacy and safety endpoints.^[223] A 2017 analysis estimated that 44% of clinical trials, including those for vaccines, contained flawed data such as statistical errors or duplications, often undisclosed due to proprietary controls over raw datasets.^[224] While regulatory bodies like the FDA have intensified efforts to mandate timely reporting to platforms such as ClinicalTrials.gov, compliance gaps persist, with negative or null results underrepresented, potentially biasing meta-analyses and overestimating benefits.^[225]^[226] Industry-funded trials dominate vaccine development, comprising the majority of evidence submitted for approvals, yet full protocols and adverse event datasets are rarely released proactively, as evidenced by calls from scientific bodies for "radical transparency" to rebuild public trust amid perceptions of withheld information.^[227]

Economic Analysis

Direct Medical Costs and Savings

Direct medical costs of immunization programs encompass vaccine procurement, storage and cold chain maintenance, administration by healthcare providers, and monitoring for adverse events. These costs vary by vaccine type, program scale, and setting; for instance, routine childhood vaccines in the United States involve expenditures on biologics and delivery infrastructure that can range from $10 to $200 per dose depending on the antigen and logistics.^[6] In low- and middle-income countries, additional expenses arise from supply chain challenges, with per-child intervention costs reported as low as $0.10 for basic outreach but up to $537 for comprehensive efforts.^[228] Despite these upfront investments, immunization yields significant direct medical savings by averting disease-related treatments, hospitalizations, and complications. A 2024 analysis of U.S. routine childhood vaccinations for birth cohorts from 1994 to 2023 estimated $780 billion in direct cost savings through prevented morbidity and mortality across diseases like measles, polio, and pertussis, far exceeding program costs.^[229] Similarly, rotavirus vaccination in low-income countries has demonstrated cost-effectiveness by reducing diarrheal hospitalizations, with incremental cost-effectiveness ratios supporting net savings when vaccine prices are below $5 per dose.^[230] For specific pathogens, such as COVID-19, vaccination programs have offset expenses through avoided intensive care; one U.S. study quantified $895 billion in direct healthcare savings from reduced cases and severity.^[231] Overall, peer-reviewed evaluations consistently show that for most routine vaccines, benefits in curtailed medical interventions— including antibiotics, ventilatory support, and long-term sequelae management—generate returns where savings exceed costs by factors of 3:1 or higher in direct terms, though outcomes depend on coverage rates above 80% to achieve herd immunity thresholds.^[232] These figures underscore immunization's role as a cost-saving intervention, provided uptake mitigates outbreak resurgence expenses.^[229]

Societal Externalities and Return on Investment

Vaccination programs produce positive externalities by conferring indirect protection to unvaccinated individuals through reduced pathogen transmission, a phenomenon central to herd immunity.^[233] High coverage levels interrupt chains of infection, safeguarding vulnerable groups such as infants too young for vaccination and those with medical contraindications or compromised immune systems.^[234] For highly transmissible diseases like measles, herd immunity requires vaccination coverage of approximately 95% to prevent outbreaks.^[8] These externalities lower overall disease incidence, reducing healthcare demands and societal productivity losses beyond the direct benefits to vaccine recipients.^[235] Economic evaluations quantify these benefits in return-on-investment (ROI) metrics, incorporating both private gains and public spillovers. In the United States, routine childhood immunizations for cohorts born 1994–2023 averted 508 million illnesses, 32 million hospitalizations, and 1.1 million deaths, generating $2.7 trillion in societal cost savings and a benefit-cost ratio of 10.9—meaning $10.90 saved per dollar invested.^[229] This analysis accounts for externalities via diminished transmission and herd effects, which amplify averted cases in the broader population.^[229] In low- and middle-income countries, immunization against 10 key pathogens (including measles, polio, and rotavirus) from 2011–2030 delivered an ROI of 22.2 using cost-of-illness methods (factoring treatment costs, caregiver time, and productivity) and 51.8 via value-of-statistical-life approaches (valuing lives saved).^[236] Measles vaccination contributed disproportionately due to its high infectivity and herd immunity dynamics.^[236] Globally, every dollar spent on vaccines has yielded up to $44 in returns through prevented morbidity, mortality, and associated economic burdens.^[237] These figures underscore immunization as a high-yield public health intervention, though realizations depend on sustained coverage to maintain externalities.^[238]

Critiques of Economic Modeling Assumptions

Economic models assessing the cost-effectiveness of immunization programs often employ dynamic transmission models to incorporate herd immunity effects, yet these rely on assumptions about vaccine efficacy, duration of protection, and population mixing patterns that introduce substantial uncertainty. For instance, vaccine efficacy estimates derived from randomized controlled trials frequently overestimate real-world performance due to differences in adherence and population characteristics, with trial efficacy for recombinant zoster vaccine reaching 96% under controlled conditions compared to 80-86% in observational settings. Similarly, limited long-term trial data—typically spanning only 4-8 years—necessitates extrapolations for protection duration, which can vary ICERs dramatically; for recombinant zoster vaccine, assumptions of lifelong protection yield $8,500 per QALY gained, while shorter durations escalate it to $89,100 per QALY.^[239] Critiques highlight the sensitivity of model outcomes to epidemiological parameters, particularly herd immunity thresholds calculated via basic reproduction number (R0), which assume homogeneous mixing and single-vaccine scenarios but falter in multi-vaccine or variant-diverse contexts. The classic threshold formula, p^c = 1 - 1/R_0, adjusted for efficacy, over-simplifies by ignoring heterogeneous contact networks and combined vaccine effects, potentially misestimating required coverage levels and thus inflating projected indirect benefits. In low- and middle-income countries, inclusion of herd effects in cost-effectiveness analyses can shift incremental cost-effectiveness ratios below willingness-to-pay thresholds in up to 45% of cases where static models (excluding them) deem interventions unfavorable, underscoring how assumption-driven herd modeling amplifies perceived value without robust validation of transmission dynamics.^[240]^[241]^[242] Additional flaws pertain to unmodeled ecological feedbacks, such as pathogen serotype replacement following vaccination, which erodes long-term efficacy gains; post-introduction of 7-valent pneumococcal conjugate vaccine, non-vaccine serotypes rose, complicating incidence projections and potentially overstating net benefits in models assuming stable disease burdens. Parameter uncertainty in costs, including adverse event probabilities and discounting rates over extended horizons, further exacerbates variability, with methodological choices like static versus dynamic modeling altering conclusions on fiscal impacts—static approaches underestimate indirect protection, while dynamic ones amplify it under optimistic transmission assumptions. These sensitivities, compounded by reliance on modeled rather than empirical long-term data, render many evaluations vulnerable to bias toward favorable outcomes, as small perturbations in inputs can invert cost-effectiveness verdicts.^[243]^[239]

Demographic and Biological Variations

Age, Sex, and Health Status Differences

Vaccine immunogenicity and efficacy vary significantly with age due to immunosenescence, which diminishes T-cell and B-cell function in older individuals, leading to reduced antibody titers and cellular responses compared to younger adults. For instance, systematic reviews of COVID-19 vaccines indicate that adults over 65 years exhibit lower neutralizing antibody levels post-vaccination than those under 65, though protection against severe outcomes remains substantial, with efficacy rates often exceeding 80% against hospitalization in elderly cohorts.^[244]^[245] In contrast, younger age at initial vaccination can impair long-term protection for certain vaccines; a study on measles vaccination found that doses administered before 9 months of age result in lower seropositivity rates and higher vaccine failure risks even after a second dose.^[246] Adolescents aged 12-15 years, however, demonstrate robust responses, with mRNA COVID-19 vaccines eliciting higher geometric mean titers than in 16-25-year-olds.^[247] Biological sex influences immune responses to immunization, with females typically generating stronger humoral and cellular immunity than males, attributed to X-chromosome-linked genes enhancing antigen presentation and hormonal factors like estrogen promoting Th2-biased responses. Meta-analyses of randomized trials confirm statistically significant sex differences, where females achieve higher antibody responses to vaccines such as influenza and hepatitis, alongside increased vaccine effectiveness in preventing infection.^[248]^[249] This disparity extends to reactogenicity, as females report more frequent local and systemic adverse events post-vaccination, potentially linked to heightened innate immunity.^[245]^[250] In older adults, seasonal influenza vaccines show higher immunogenicity and effectiveness in females versus males, underscoring the need for sex-stratified efficacy assessments.^[251] Health status profoundly affects immunization outcomes, particularly in immunocompromised individuals, where impaired adaptive immunity results in suboptimal seroconversion rates—often below 50% for standard doses of inactivated vaccines like influenza or pneumococcal. Guidelines from bodies such as the CDC and ASCO recommend additional doses or higher antigen formulations for moderately to severely immunocompromised patients, including those with malignancies, organ transplants, or primary immunodeficiencies, to improve response thresholds.^[252]^[253] Live attenuated vaccines are generally contraindicated in such groups due to risks of uncontrolled replication, while timing vaccination prior to immunosuppressive therapy—ideally two weeks beforehand—maximizes efficacy.^[254] Systematic reviews categorize responses into low, moderate, or high seroconversion based on immunosuppression degree, with solid organ transplant recipients showing particularly diminished protection against respiratory pathogens.^[252] Despite reduced immunogenicity, vaccination remains beneficial for mitigating severe disease in these populations.^[255]

Genetic and Ethnic Influences on Response

Genetic variations in immune-related genes significantly influence vaccine-induced immune responses, including antibody production and cellular immunity. The human leukocyte antigen (HLA) system, characterized by high polymorphism, is a primary genetic determinant, with specific alleles modulating recognition of vaccine antigens and subsequent T-cell activation. For instance, HLA class II alleles such as HLA-DRB1, HLA-DPB1, and HLA-DQB1 have been associated with variations in antibody responses to measles, hepatitis B, and SARS-CoV-2 vaccines.^[256]^[257] Polymorphisms in cytokine genes, like those encoding tumor necrosis factor-alpha (TNF-α), and pattern recognition receptors such as Toll-like receptor 4 (TLR4), further affect antibody titers; for example, certain TLR4 variants correlate with reduced responses to pertussis vaccines.^[258]^[259] These genetic factors contribute to inter-individual variability, where some individuals achieve robust, long-lasting immunity while others exhibit hyporesponsiveness or non-response. Genome-wide association studies have identified loci beyond HLA, including those involved in B-cell activation and interferon signaling, that predict post-vaccination seroconversion rates. In hepatitis B vaccination, polymorphisms in genes regulating immune signaling explain up to 40-60% of the heritability in antibody levels.^[260]^[261] Such variations underscore the limitations of one-size-fits-all vaccination strategies, as host genetics can alter vaccine efficacy independently of pathogen or adjuvant factors.^[131] Ethnic differences in vaccine responses often stem from varying frequencies of these genetic alleles across populations, leading to population-level disparities in immunogenicity. Children of African descent, including Somali Americans, produce approximately twice the rubella-specific antibodies compared to Caucasians following measles-mumps-rubella vaccination, linked to higher frequencies of protective HLA alleles.^[262] Conversely, indigenous populations, such as certain aboriginal groups in Taiwan, exhibit significantly lower anti-hepatitis B surface antigen titers, potentially due to underrepresentation of high-responder alleles.^[263] For SARS-CoV-2 mRNA vaccines, HLA allele distributions contribute to observed ethnic variations in antibody persistence, with alleles more common in European ancestries associated with stronger responses in some cohorts.^[264] Limited ethnic diversity in clinical trials exacerbates uncertainties, as allele frequencies differ globally; for example, trials with under 10% African-American or Asian participants may overestimate efficacy in underrepresented groups.^[265] These findings highlight the need for pharmacogenomic approaches to tailor vaccination, though environmental and health status confounders must be controlled in interpreting ethnic effects. Peer-reviewed studies, often from diverse cohorts, provide robust evidence, contrasting with less reliable anecdotal reports.^[266]

Policy and Implementation

Government Programs and Legal Mandates

In the United States, the Vaccines for Children (VFC) program, established in 1994 under the Omnibus Budget Reconciliation Act, provides no-cost vaccines to eligible children up to age 19 who are uninsured, Medicaid-eligible, American Indian, or Alaskan Native.^[267] This federally funded initiative, administered by the Centers for Disease Control and Prevention (CDC), covers all Advisory Committee on Immunization Practices (ACIP)-recommended vaccines and has enrolled over 40,000 providers nationwide to increase immunization rates among underserved populations.^[267] State health departments oversee local implementation, ensuring vaccines are stored and administered according to federal guidelines without charge to families.^[268] All 50 states and the District of Columbia mandate specific vaccines for school and childcare entry, typically including measles, mumps, rubella, diphtheria, tetanus, pertussis, polio, hepatitis B, and varicella, with requirements varying by age and setting.^[269] Medical exemptions are universally permitted when a physician certifies contraindications, while 45 states and the District of Columbia allow religious exemptions and 15 permit philosophical or personal belief exemptions as of May 2025.^[270] Recent legislative activity, including over 370 vaccine-related bills introduced in 44 states by early 2025, reflects ongoing debates, with some states like Florida announcing plans to phase out certain childhood vaccine mandates in September 2025 amid concerns over parental rights and post-pandemic trust erosion.^[271] ^[272] The U.S. Supreme Court's 1905 decision in Jacobson v. Massachusetts established the constitutional basis for state vaccine mandates, upholding a Cambridge, Massachusetts, ordinance requiring smallpox vaccination during an outbreak and imposing a $5 fine for noncompliance, as a valid exercise of police power to protect public health.^[203] The ruling affirmed that individual liberties yield to community welfare when vaccination demonstrates reasonable necessity and proportionality, though it did not endorse forced administration, limiting enforcement to fines or quarantine.^[203] This precedent has influenced subsequent rulings but faces scrutiny in modern contexts, with courts occasionally striking down mandates lacking evidence of imminent threat or adequate exemptions.^[273] Globally, the World Health Organization's Expanded Programme on Immunization (EPI), launched in 1974, guides national programs to vaccinate against priority diseases like tuberculosis, diphtheria, pertussis, tetanus, polio, and measles, achieving coverage for over 80% of infants in many countries by 2024.^[274] National efforts, such as routine immunization schedules integrated into public health systems, have contributed to eradicating smallpox and nearly eliminating polio, with WHO-supported introductions of vaccines like HPV in 147 countries by 2024.^[275] Legal mandates vary; for instance, many nations enforce school-entry requirements similar to the U.S., while others like Brazil and India conduct mass campaigns with compulsory elements during outbreaks, backed by international funding from GAVI and UNICEF.^[276] These programs have averted an estimated 154 million deaths since 1974, predominantly infants, though coverage gaps persist in low-income regions due to logistical and enforcement challenges.^[277]

Addressing Vaccine Hesitancy and Public Trust

Vaccine hesitancy, defined as delay in acceptance or refusal of vaccines despite availability of vaccination services, has persisted as a global challenge, with empirical data indicating rates varying by region and vaccine type. In the United States, a 2025 survey revealed that confidence in the safety of measles, mumps, and rubella (MMR) vaccines stood at 83%, while trust in flu vaccines was lower at 74%, reflecting broader declines linked to perceived institutional inconsistencies during the COVID-19 pandemic. Factors driving hesitancy include concerns over side effects, with studies identifying these as the most frequent reason, alongside distrust in pharmaceutical companies and health authorities, exacerbated by historical events and rapid vaccine development timelines.^[278]^[279]^[280] Public trust in vaccination programs has eroded notably in recent years, particularly post-2020, with U.S. polls showing a drop in strong agreement with CDC vaccine recommendations from 51% to 39% between 2020 and 2025, attributed to shifts in perceptions of agency reliability amid policy changes and communication lapses. Internationally, UNICEF data from 2023-2025 highlighted declining confidence in childhood vaccines by up to 44 percentage points in some areas, driven by service disruptions, misinformation proliferation, and waning faith in expertise, leading to 67 million children missing vaccinations. Among healthcare workers, a 2022-2023 survey of over 2,000 respondents found hesitancy correlated with lower trust in safety data and institutional motives, underscoring how professional skepticism mirrors public trends.^[281]^[282]^[283] Coercive measures, such as mandates, have demonstrated counterproductive effects on trust, with analyses of COVID-19 policies revealing increased polarization, reduced vaccine confidence, and heightened resistance, as individuals exhibited psychological reactance against perceived overreach. In contrast, transparency in disclosing safety data, including rare adverse events, sustains long-term trust by mitigating suspicions, as evidenced by studies showing that open communication about negative features—while potentially causing short-term uptake dips—prevents broader erosion when paired with rigorous monitoring systems like the Vaccine Safety Datalink. Peer-reviewed evaluations emphasize that multicomponent interventions, including dialogue-based communication and community engagement via trusted local figures, outperform unidirectional messaging, with systematic reviews confirming modest improvements in uptake through personalized discussions addressing specific concerns rather than blanket reassurances.^[284]^[285]^[286] Efforts to rebuild trust necessitate addressing root causes empirically, such as enhancing data accessibility from systems monitoring post-licensure events, which have successfully identified signals like intussusception risks for rotavirus vaccines, thereby informing refinements without undermining overall programs. Critiques of overly optimistic economic models or dismissal of hesitancy as mere "anti-science" ignore causal links to opaque trial data releases, as seen in delays for COVID-19 vaccine datasets, which fueled perceptions of withheld information. Prioritizing independent audits and public engagement over shaming or censorship aligns with evidence that building credibility requires acknowledging uncertainties, like variable efficacy against transmission, to foster informed consent rather than compliance through authority.^[163]^[223]^[287]

Global Access Challenges and Equity

Global immunization coverage exhibits stark disparities between high-income and low-income countries, with the latter facing persistent barriers to achieving equitable access. In 2024, approximately 14.3 million children worldwide—predominantly in low- and middle-income countries—remained zero-dose, meaning they received no vaccinations at all, according to World Health Organization (WHO) and UNICEF estimates.^[275] Coverage for the third dose of the diphtheria-tetanus-pertussis (DTP3) vaccine, a key indicator of immunization system performance, stood at around 84% globally but fell short of the 95% threshold needed to prevent outbreaks, with rates significantly lower in regions like sub-Saharan Africa due to systemic access issues.^[288] These gaps highlight how wealthier nations achieve near-universal coverage while poorer ones struggle, exacerbating disease burdens in vulnerable populations.^[289] Key challenges include inadequate infrastructure, such as unreliable cold chains and transportation networks essential for vaccine viability in remote or rural areas of developing countries.^[290] Supply chain disruptions, compounded by geographic isolation and conflict zones, further hinder distribution, as seen in fragile states where delivery delays prevent timely immunization.^[291] Funding volatility poses another barrier; for instance, the United States' decision in July 2025 to halt contributions to Gavi, the Vaccine Alliance—which has supported immunization in low-income countries since 2000—threatens sustainability, given Gavi's role in protecting over 1 billion children and averting 17.3 million future deaths.^[292] ^[7] Health workforce shortages and limited local manufacturing capacity in the developing world also perpetuate dependence on imported vaccines, restricting self-reliance and rapid response to outbreaks.^[293] ^[294] Geopolitical factors, including international sanctions, have been empirically linked to reduced child immunization rates in affected developing nations by disrupting supply lines and economic stability.^[295] Despite initiatives like Gavi, which enabled access to vaccines for 72 million children in lower-income countries in 2024 alone, transitioning middle-income countries often face financing gaps and decision-making hurdles post-donor support, underscoring the limits of external aid in fostering equitable, self-sustaining systems.^[296] ^[297] Efforts to address these inequities require bolstering domestic capacities, yet persistent underinvestment and external dependencies continue to widen the global divide in immunization outcomes.^[298]

References

[1]
Immunization - StatPearls - NCBI Bookshelf - NIH
When a disease-causing bacterium or virus invades the human body, the immune system recognizes the material as foreign, usually by detecting specific protein ...
[2]
Introduction - PMC - NIH
Dec 12, 2014 · Vaccines by definition are biological agents that elicit an immune response to a specific antigen derived from an infectious disease-causing ...
[3]
A guide to vaccinology: from basic principles to new developments
Dec 22, 2020 · This Review provides an introductory overview of vaccines, immunization and related issues and thereby aims to inform a broad scientific audience
[4]
Edward Jenner and the history of smallpox and vaccination - NIH
Edward Jenner (Figure 1) is well known around the world for his innovative contribution to immunization and the ultimate eradication of smallpox.
[5]
History of smallpox vaccination - World Health Organization (WHO)
Vaccination led to smallpox elimination in western Europe, North America and Japan. In the absence of a large-scale coordinated international programme, the ...
[6]
Impact of Vaccines; Health, Economic and Social Perspectives - PMC
Jul 14, 2020 · Reduction in Infectious Diseases Morbidity and Mortality. The most significant impact of vaccines has been to prevent morbidity and mortality ...
[7]
Global immunization efforts have saved at least 154 million lives ...
Apr 24, 2024 · The study found that for each life saved through immunization, an average of 66 years of full health were gained – with a total of 10.2 billion ...Missing: empirical | Show results with:empirical
[8]
How Herd Immunity Works | History of Vaccines
Feb 22, 2025 · Herd immunity—sometimes called community immunity—is like a shield that protects everyone in a group, even those who can't protect themselves ...
[9]
Principal Controversies in Vaccine Safety in the United States
We summarize the key evidence on some of the main current vaccine safety controversies in the United States, including (1) measles, mumps, and rubella vaccine ...
[10]
Vaccine Safety: Myths and Misinformation - Frontiers
In this article we summarize common vaccine safety controversies and highlight what we feel are some of the most important studies refuting these concerns.
[11]
Vaccine hesitancy: An overview - PMC - PubMed Central
Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics.
[12]
Impact of Routine Childhood Immunization in Reducing Vaccine ...
Aug 22, 2022 · Routine immunization reduced the incidence of all targeted diseases, leading to reductions in incidence ranging from 17% (influenza) to 100% ( ...
[13]
Chapter 1: Principles of Vaccination | Pink Book - CDC
Mar 22, 2024 · Vaccines contain antigens that stimulate the immune system to produce an immune response that is often similar to that produced by the natural ...Missing: core | Show results with:core
[14]
How do vaccines work? - World Health Organization (WHO)
Feb 25, 2025 · Vaccines use weakened antigens to trigger an immune response, without causing disease, and may use multiple doses to build memory cells.
[15]
Fundamentals of Vaccine Immunology - PMC - NIH
Vaccine immunology includes the immune system, passive/active immunization, how immunizations stimulate immunity, and the types of vaccines available.
[16]
Immunity Types | Vaccines & Immunizations - CDC
Jul 30, 2024 · The major advantage to passive immunity is that protection is immediate, whereas active immunity takes time (usually several weeks) to develop. ...
[17]
Passive Immunization: Toward Magic Bullets - PMC - PubMed Central
Passive immunity provides immediate but short-lived protection, lasting several weeks up to 3 or 4 months. Passive immunity can occur naturally, when maternal ...
[18]
Passive and active immunity in infants born to mothers with SARS ...
May 3, 2021 · Updated version available: A peer-reviewed version of this article, "Passive and active immunity in infants born to mothers with SARS-CoV-2 ...
[19]
“Herd Immunity”: A Rough Guide | Clinical Infectious Diseases
Simple threshold concept of herd immunity. A, Relationship between the herd immunity threshold, (R0 – 1)/R0 = 1 − 1/R0,and basic reproduction number, R0, in a ...Abstract · HISTORY · EPIDEMIOLOGIC... · THEORETICAL...Missing: peer | Show results with:peer
[20]
Onward Virus Transmission after Measles Secondary Vaccination ...
Aug 9, 2024 · Measles virus is one of the most infectious pathogenic agents and has a basic reproduction number (R0) of 12–18, indicating that each infected ...
[21]
Complexity of the Basic Reproduction Number (R0) - CDC
Nov 27, 2018 · R0 values have been published for measles, polio, influenza, Ebola virus disease, HIV disease, a diversity of vectorborne infectious diseases, ...
[22]
Measles Cases and Outbreaks - CDC
The measles, mumps, and rubella (MMR) vaccine is very safe and effective. When more than 95% of people in a community are vaccinated (coverage >95%), most ...
[23]
A mathematical model reveals the influence of population ... - Science
Jun 23, 2020 · The classical herd immunity level hC is defined as hC = 1 – 1/R0, where R0 is the basic reproduction number, defined as the average number of ...Missing: formula | Show results with:formula
[24]
Influence of heterogeneous age-group contact patterns on critical ...
Feb 16, 2022 · In this paper, we have assumed a limited supply of vaccines conferring waning immunity to deal with some of these issues. The aim is to see how ...
[25]
SIRS epidemics with individual heterogeneity of immunity waning
Jun 21, 2024 · Herd immunity requires more frequent vaccination when heterogeneity is considered. •. Larger amount of vaccine supply is needed when ...
[26]
Falling Vaccination Rates Threaten Herd Immunity: The Role of ...
Sep 9, 2025 · She noted that with national vaccination rates falling below the 95% threshold for herd immunity—down to 92.7% in 2023-2024 and as low as 80% to ...
[27]
Measles Vaccination Coverage After a Postelimination Outbreak
Sep 24, 2025 · In the World Health Organization Region of the Americas, measles vaccination coverage must exceed 93% to maintain herd immunity. Although the ...Missing: real examples
[28]
First Widespread Smallpox Inoculations | Research Starters - EBSCO
The first widespread smallpox inoculations emerged in seventeenth-century China, building on earlier practices that date back to the Song Dynasty in the tenth ...<|separator|>
[29]
Vaccine Timeline Before Jenner and After COVID-19
According to researchers, inoculation with materials from smallpox lesions to trigger immunity against smallpox dates back to antiquity in China. And the first ...
[30]
History of Smallpox - CDC
Oct 23, 2024 · One of the first methods for controlling smallpox was variolation, a process named after the virus that causes smallpox (variola virus).
[31]
The origins of inoculation - PMC - PubMed Central - NIH
Early in the 18th century, variolation (referred to then as 'inoculation') was introduced to Britain and New England to protect people likely to be at risk ...
[32]
Variolation - Smallpox - National Library of Medicine - NIH
By 1700, variolation had spread to Africa, India and the Ottoman Empire. In contrast to Asians and Africans who inoculated by blowing dried smallpox scabs up ...
[33]
The History of Variolation - HistoryOfVaccines.org
Jun 5, 2021 · By the time Edward Jenner discovered vaccination with cowpox to prevent smallpox in 1796, variolation had been more widely accepted than ever.
[34]
A Brief History of Vaccination - World Health Organization (WHO)
In May 1796, English physician Edward Jenner expands on this discovery and inoculates 8-year-old James Phipps with matter collected from a cowpox sore on ...History of smallpox vaccination · History of polio vaccination
[35]
Edward Jenner, FRS FRCPE | History of Vaccines
In May 1796, a British physician named Edward Jenner tested his hypothesis that direct inoculation of a person with the much milder and less deadly cowpox ...
[36]
Louis Pasteur, ForMemRS | History of Vaccines
1880. Rabies Studies Begin ; June 5, 1881. Landmark Anthrax Vaccine Study ; 1884. Attenuating the Rabies Virus ; May 19, 1884. Rabies Success with Dogs Announced.Missing: key century<|separator|>
[37]
Louis Pasteur: A Legacy Unmasked - PMC - NIH
Aug 29, 2024 · Louis Pasteur's creation of vaccines for anthrax and rabies was instrumental in showcasing the power of immunization and its role in disease ...Missing: 19th | Show results with:19th
[38]
Richard Pfeiffer's typhoid vaccine and Almroth Wright's claim to priority
Apr 8, 2021 · In December 1895, Wright had been commissioned by the Army Medical Department to develop a typhoid vaccine and he later admitted that such work ...
[39]
Waldemar Mordecai Haffkine, CIE (1860-1930) - PubMed
Waldemar Mordecai Haffkine developed an anticholera vaccine at the Pasteur Institute, Paris, in 1892. From the results of field trials in India from 1893 to ...
[40]
Vaccines: Past, Present, and Future - NCBI - NIH
The first definitive experiments with pertussis vaccine were conducted in the 1920s. Because the portions of the pertussis organism responsible for clinical ...
[41]
Two centuries of vaccination: historical and conceptual approach ...
Years later, in 1921, Albert Calmette and Camille Guérin developed the Bacille Calmette-Guérin (BCG) vaccine based on an attenuated strain of Mycobacterium ...
[42]
1955 Polio Vaccine Trial Announcement
The Salk vaccine has been proved to be up to 80-90 percent effective in preventing paralytic polio.
[43]
The day polio met its match: Celebrating 70 years of the Salk vaccine
Apr 11, 2025 · The polio vaccine developed by Jonas Salk and colleagues was officially declared “safe, effective, and potent”—a moment heralded as a triumph of ...
[44]
History of polio vaccination - World Health Organization (WHO)
The first successful vaccine was created by US physician Jonas Salk. Salk tested his experimental killed-virus vaccine on himself and his family in 1953.
[45]
History of Measles - CDC
May 9, 2024 · In 1963, John Enders and colleagues transformed their Edmonston-B strain of measles virus into a vaccine and licensed it in the United States. ...
[46]
Smallpox Eradication Programme - SEP (1966-1980)
May 1, 2010 · Smallpox was officially declared eradicated in 1980 and is the first disease to have been fought on a global scale.Missing: timeline | Show results with:timeline
[47]
The Spread and Eradication of Smallpox: An Overview - CDC
Oct 23, 2024 · After a global eradication campaign that lasted more than 20 years, the 33rd World Health Assembly declares the world free of smallpox in 1980.
[48]
The contribution of vaccination to global health: past, present and ...
Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated.
[49]
Vaccine History Timeline - Immunize.org
An acellular pertussis vaccine combined with the adult formulation of tetanus and diphtheria (Tdap: Boostrix by GSK) was licensed for use as an active ...
[50]
First recombinant DNA vaccine for HBV - Nature
Sep 28, 2020 · It was the first vaccine to be produced using recombinant DNA technology and although it was only the third recombinant product to be approved for clinical use.
[51]
Vaccine History: Developments by Year
Aug 21, 2023 · Because of successful eradication efforts, the smallpox vaccine was no longer recommended for use after 1972. While vaccine research ...
[52]
About Pneumococcal Vaccines: For Providers - CDC
FDA licensed the first pneumococcal conjugate vaccine (PCV7) in 2000. A large clinical trial showed PCV7 reduced invasive disease caused by vaccine serotypes by ...
[53]
Whooping cough - Outbreaks and vaccine timeline - Mayo Clinic
1991. The diphtheria-tetanus-acellular pertussis (DTaP) vaccine is licensed. This vaccine is an acellular vaccine, which causes fewer side effects ...Missing: BCG | Show results with:BCG<|separator|>
[54]
Chapter 22: Varicella | Pink Book - CDC
May 9, 2024 · Varicella vaccine was licensed for general use in Japan and Korea in 1988, and in the United States in 1995 for persons age 12 months or older.
[55]
The HPV Vaccine: Access and Use in the U.S. - KFF
Aug 5, 2024 · The FDA approved first-generation Gardasil®—produced by Merck—in 2006, which prevented infection of four strains of HPV: 6, 11, 16, and 18.
[56]
Vaccines for the 21st century - PMC - NIH
This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer.Introduction · Selected Clinical Trials On... · Enabling Technologies For...
[57]
Vaccine Types - HHS.gov
Dec 22, 2022 · Inactivated vaccines use the killed version of the germ that causes a disease. Inactivated vaccines usually don't provide immunity (protection) ...Missing: efficacy | Show results with:efficacy
[58]
Inactivated Viral Vaccines - PMC - NIH
Inactivated vaccines have been used for over a century to induce protection against viral pathogens. This established approach of vaccine production is ...
[59]
Vaccine Technologies and Platforms for Infectious Diseases
Inactivated vaccines are derived from a killed form of virulent pathogens and typically stimulate an antibody-mediated immune response. The inactivation process ...
[60]
The history of vaccination
This saw the first inactivated vaccines be developed to protect people from infection with typhoid and cholera bacteria in 1896.
[61]
Different Types of Vaccines - HistoryOfVaccines.org
Feb 24, 2025 · Inactivated Vaccines: Safety Through Sterilization. Inactivated vaccines use killed pathogens, making them safer for vulnerable populations.
[62]
History and evolution of influenza control through vaccination - NIH
The efficacy and safety of inactivated vaccines were first studied between 1942 and 1945; in the meantime, a new strain of flu virus was discovered, the ...
[63]
Understanding Six Types of Vaccine Technologies - Pfizer
Inactivated vaccines take a live pathogen and inactivate or kill it. When the vaccine is then introduced to a human through a shot, for example, the inactivated ...Missing: efficacy | Show results with:efficacy
[64]
Safety and Efficacy of the Different Types of Vaccines
Oct 15, 2024 · Inactivated vaccines use viruses or bacteria that have been killed or inactivated. These vaccines cannot cause the disease they protect against ...Missing: definition | Show results with:definition
[65]
Immunological mechanisms of vaccination - PMC - PubMed Central
The first group, live attenuated vaccines, comprises weakened versions of the pathogens; these mimic the kind of protective immunity induced in people who ...
[66]
Explaining How Vaccines Work - CDC
Aug 10, 2024 · Either way, active immunity takes longer to develop but lasts longer than passive immunity. Passive immunity is provided by antibodies produced ...
[67]
Viral Live‐Attenuated Vaccines (LAVs): Past and Future Directions
Dec 6, 2024 · Currently, live attenuated vaccines (LAVs) remain the most efficacious and widely utilized tool for combating viral infections.Missing: definition | Show results with:definition
[68]
The development of vaccines: how the past led to the future - Nature
Oct 3, 2011 · In the 1960s, three classical attenuated-virus vaccines were developed: against measles virus, by Samuel Katz and John Enders; mumps virus, by ...
[69]
Life-threatening infections due to live attenuated vaccines
Live attenuated vaccines (LAVs) can protect humans against 12 viral and three bacterial diseases. By definition, any clinical infection caused by a LAV that ...
[70]
Transmissible Viral Vaccines - PMC - PubMed Central - NIH
Being live, these vaccines are, in principle, capable of transmission to new hosts, although perhaps at a far reduced level compared to viruses capable of ...Attenuated Vaccines · Properties Of Transmissible... · Figure 1
[71]
Live attenuated vaccines: Historical successes and current challenges
Many other vaccines both killed (Salk, 1953) and live were explored in the 1950s and the inactivated vaccine of Salk in its modern form is playing an increasing ...<|control11|><|separator|>
[72]
Rationalizing the development of live attenuated virus vaccines - PMC
Classically attenuated viruses, those created by passaging a virus in cultured cells, have proven to be an effective means for preventing many viral diseases, ...Missing: definition | Show results with:definition
[73]
Vaccine Types | NIAID
Jul 1, 2019 · Instead of the entire pathogen, subunit vaccines include only the components, or antigens, that best stimulate the immune system. Although this ...
[74]
Platforms for Production of Protein-Based Vaccines - PubMed Central
The first subunit vaccine against hepatitis B virus (HBV) was approved in 1986 and was based on the viral surface protein that self-assembled into VLPs using S.
[75]
COVID-19 Vaccine Basics - CDC
Sep 3, 2024 · Protein subunit COVID-19 vaccines are given in the upper arm muscle. After vaccination, nearby cells pick up these proteins. Next, our immune ...
[76]
Diphtheria - StatPearls - NCBI Bookshelf - NIH
Feb 26, 2024 · Vaccines for diphtheria are formulated as toxoids, which are denatured proteins (bacterial toxins) with an intact receptor binding site capable ...Introduction · Epidemiology · History and Physical · Evaluation<|separator|>
[77]
Tetanus (Clostridium tetani Infection) - StatPearls - NCBI Bookshelf
Feb 26, 2024 · The tetanus toxoid vaccine was first produced in 1924 and used extensively among soldiers during World War II. The pentavalent vaccine, which ...
[78]
Chapter 7: Diphtheria | Pink Book - CDC
Apr 23, 2024 · Diphtheria toxoid was developed in the early 1920s but was not widely used until the early 1930s. It was incorporated with tetanus toxoid and ...Missing: mechanism | Show results with:mechanism
[79]
Tetanus Toxoid - StatPearls - NCBI Bookshelf - NIH
The tetanus toxoid is a vaccine used in the management and treatment of tetanus. It is in the vaccine class of medications.
[80]
Conjugate vaccines - PMC - NIH
Adult responses to pneumococcal polysaccharides are dominated by IgG2, but both IgG1 and IgG2 are mounted to pneumococcal conjugate vaccines in adults [22,23].
[81]
Chapter 8: Haemophilus influenzae | Pink Book - CDC
May 21, 2024 · The first Hib conjugate vaccine was licensed in 1987. Conjugation is ... Hib Vaccine Efficacy. Highly immunogenic; More than 95% of ...Secular Trends In The United... · Hib Secular Trends In The... · Vaccination Schedule And Use
[82]
Triumph of Pneumococcal Conjugate Vaccines: Overcoming a ... - NIH
Sep 30, 2021 · A vaccine made from attaching polysaccharide from Hib to a carrier protein was introduced to the market in 1987. This vaccine was highly ...
[83]
Polysaccharide and conjugate vaccines to Streptococcus ... - NIH
Aug 3, 2022 · Two pneumococcal vaccines containing S. pneumoniae capsular polysaccharides are in current use: the polysaccharide vaccine PPSV23 and the ...Missing: Hib examples
[84]
A Comprehensive Review of mRNA Vaccines - PMC - NIH
Jan 31, 2023 · In this review we have summarized each and every aspect of the mRNA vaccine. The article describes the mRNA structure, its pharmacological ...
[85]
Recent Advancement in mRNA Vaccine Development and ... - NIH
Jul 18, 2023 · In this review, we shed light on different types of mRNA vaccines, their mode of action, and the process to optimize their development and ...
[86]
The tangled history of mRNA vaccines - Nature
Sep 14, 2021 · In late 1987, Robert Malone performed a landmark experiment. He mixed strands of messenger RNA with droplets of fat, to create a kind of molecular stew.Missing: mechanism | Show results with:mechanism
[87]
The Long History of mRNA Vaccines | Johns Hopkins
Oct 6, 2021 · Messenger RNA, or mRNA, was discovered in the early 1960s; research into how mRNA could be delivered into cells was developed in the 1970s.Missing: mechanism peer- reviewed
[88]
mRNA Vaccine Technology Beyond COVID-19 - PMC - NIH
Recent advancements in mRNA design, delivery systems, and production scalability have expanded its applications to oncology, autoimmune disorders, and genetic ...
[89]
Comparative safety analysis of mRNA and adenoviral vector COVID ...
Although rare, the risk of myocarditis or pericarditis was higher with mRNA-based vaccines than with adenoviral vector vaccines, particularly in young ...
[90]
Revolutionizing immunization: a comprehensive review of mRNA ...
Mar 12, 2025 · This review provides a comprehensive analysis of the mRNA vaccine technology, detailing the structure of the mRNA vaccine and its mechanism of action in ...
[91]
Viral Vector Vaccine Development and Application during the ... - NIH
Viral vector vaccines have several unique advantages compared to other vaccine platforms. The spread of Omicron has also made the development of intranasal ...
[92]
Viral vector vaccines – What they are, and what they are not | CEPI
Apr 8, 2025 · Viral vector vaccines use a harmless version of a carrier virus, or vector, to deliver specific genetic instructions to human cells.Missing: mechanism review
[93]
Comparative efficacy and safety of COVID-19 vaccines in phase III ...
Feb 21, 2024 · In terms of efficacy, all vaccine types versus placebo significantly prevented symptomatic SARS-CoV-2 infection, but the 95% CI for DNA vaccines ...
[94]
Development and Applications of Viral Vectored Vaccines to ...
This review discusses the advantages and disadvantages of different viral vaccine vectors and their general strategies and applications in both human and ...
[95]
Table 1 Advantages and disadvantages of different vaccine platforms
Viral vector vaccine. Stronger immune response; Preservation of native antigen; Mimicking natural infection. More complicated manufacturing process; Risk of ...Missing: mechanism review
[96]
Safety and Efficacy of COVID-19 Vaccines: A Systematic Review ...
In terms of vaccine safety, mRNA vaccines showed more relevance to serious adverse events than viral vector and inactivated vaccines, but no solid evidence ...
[97]
Advances in Biotechnology and the Development of Novel Human ...
Sep 22, 2025 · This review explores the cutting-edge platforms—including mRNA, DNA, virus-like particles, viral and bacterial vectors, and bacteriophage-based ...
[98]
Accelerating vaccine development: Plug-and-play platforms for ... - NIH
Jun 21, 2025 · By reducing redundant testing and paperwork, “plug-and-play” platforms streamline regulatory approvals and ensure vaccines can be produced at ...
[99]
mRNA vaccines: Past, present, future - ScienceDirect
This review provides a comprehensive overview of mRNA vaccines used in past and present studies, and discusses future directions and challenges
[100]
How Vaccines are Developed and Approved for Use - CDC
Aug 10, 2024 · Phase 2. The clinical trial expands to hundreds (100-300) of trial participants who have characteristics (such as age and physical health) ...Missing: methodologies | Show results with:methodologies
[101]
Phases of clinical trials - NCIRS
In phase I clinical trials, typically dozens of participants are recruited. In this phase, the vaccine dose level and safety are tested. It takes at least 1 ...
[102]
Vaccine Development, Testing, and Regulation | History of Vaccines
Normally, vaccine development is a step-by-step process: first phase I trials, then phase II, and finally phase III. This method ensures unsuccessful vaccines ...
[103]
The clinical development process for a novel preventive vaccine
The objective is to identify the vaccine preparation, optimal dose, and schedule to be taken up for confirmatory Phase III trials. · Phase II studies assess the ...
[104]
EVALUATION OF THE 1954 POLIOMYELITIS VACCINE FIELD TRIAL
The purpose of the poliomyelitis vaccine evaluation program in the field trial of 1954 was to seek a measure of the prophylactic effect of the preparations ...
[105]
[PDF] The 1954 Field Trial of the Salk Poliomyelitis Vaccine
With 100,000 in each group, the expected numbers of polio cases would be 50 and 25, and such a result would be persuasive. In practice, a much larger study was ...<|separator|>
[106]
Jonas Salk, MD | History of Vaccines
... results of the Salk poliovirus vaccine trial. The vaccine, they said, was 80-90% effective against paralytic polio. The U.S. government licensed Salk's ...
[107]
1954 Polio Field Trial Data - Random Services
The table below gives the results of the 1954 field trials to test the Salk polio vaccine (named for the developer, Jonas Salk), conducted by the National ...
[108]
COOPERATIVE MEASLES VACCINE FIELD TRIAL : I. Clinical Efficacy
At the end of a year, efficacy had fallen to 75%. The combined vaccine schedules demonstrated a consistently high order of protection, of about 95% or better, ...
[109]
A Review of Clinical Trials of Human Papillomavirus Prophylactic ...
Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine- ...
[110]
A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna ...
Clinical trial results showed the Pfizer and Moderna vaccines to be 95.0%, and the Johnson & Johnson vaccine to be 66.0% effective in protecting against ...
[111]
Human Papillomavirus Vaccine Efficacy and Effectiveness against ...
In a real-world setting, the notable decrease of HPV 6/11/16/18 among vaccinated women compared with unvaccinated women shows the vaccine to be highly effective ...
[112]
Measles Vaccination - CDC
Jan 17, 2025 · The vaccine is safe and effective · 93% effective against measles · 72% effective against mumps · 97% effective against rubella.
[113]
Measles vaccination: Know the facts - IDSA
Two doses of MMR vaccine in childhood are about 97% effective at preventing measles, providing long-term and possibly lifelong immunity. We all want to do ...
[114]
Study shows gradual waning of MMR vaccine effectiveness over time
Sep 27, 2024 · MMR remains highly protective against measles for life, protecting over 95% of vaccinated individuals from measles. Sign in to keep reading. We' ...Missing: clinical | Show results with:clinical
[115]
'Unqualified failure' in polio vaccine policy left thousands of kids ...
May 7, 2024 · OPV has helped bring down polio cases by more than 99.9% since the eradication program began in 1988. The “wild” poliovirus is now cornered in ...
[116]
Polio: The Disease & Vaccines - Children's Hospital of Philadelphia
May 19, 2025 · Wildtype 2 was eradicated in 1999, and wildtype 3 was eradicated in 2020. Eradication means the virus no longer infects anyone anywhere in the ...
[117]
Fighting polio vaccine misinformation - GPEI
Oct 30, 2023 · Pakistan's polio eradication programme has managed several misinformation crises in the past, many of them about the polio vaccine. In October ...
[118]
HPV vaccine cuts cervical cancer cases by nearly 90%
HPV vaccine cuts cervical cancer cases by nearly 90% · Among those who received the HPV vaccine when they were 12 or 13 years old, there was an 87% reduction in ...
[119]
HPV vaccine, cervical cancer study delivers historic results | STAT
Jan 25, 2024 · HPV vaccine study finds zero cases of cervical cancer among women vaccinated before age 14.
[120]
“The power of science”: HPV vaccine proven to dramatically reduce ...
Nov 3, 2021 · The vaccine was shown to dramatically reduce cervical cancer rates by almost 90% in women in their 20s who were offered it at age 12 to 13.<|separator|>
[121]
Waning Protection after Fifth Dose of Acellular Pertussis Vaccine in ...
Sep 13, 2012 · Taken together, these studies indicate that protection is less enduring with DTaP than with whole-cell pertussis vaccines. The recent California ...
[122]
Waning Immunity to Pertussis Following 5 Doses of DTaP | Pediatrics
Apr 1, 2013 · This evaluation reports increasing risk of pertussis in the 6 years after receipt of the fifth DTaP dose, suggesting that waning of vaccine- ...
[123]
Acellular pertussis vaccines protect against disease but fail to ...
Several observational studies recently concluded that children primed with aP vaccine are at greater risk for pertussis diagnosis compared with wP-primed ...
[124]
Whole-Cell and Acellular Pertussis Vaccine: Reflections on Efficacy
Jun 13, 2022 · A cohort study in Canada showed a significant waning of immunity in those who received aP vaccine with vaccine effectiveness of 41% (95% CI: 0– ...<|separator|>
[125]
Real-world effectiveness of seasonal influenza vaccination and age ...
Mar 19, 2024 · We identified 2429 publications and included 191 in the meta-analysis. The pooled IVE was 41.4 % (95 % CI: 39.2–43.5 %) against any influenza.
[126]
Real-world effectiveness of seasonal influenza vaccination and age ...
Mar 19, 2024 · The IVE against any influenza was 48.6 % (95 % CI: 44.7-52.2 %) for children aged < 18 years, 36.7 % (95 % CI: 31.9-41.1 %) for adults aged 18- ...
[127]
Decline in Seasonal Influenza Vaccine Effectiveness With ...
The evidence suggests that influenza VE declines with vaccination PM. This study forms the basis for further discussions and examinations of the potential ...Abstract · METHODS · RESULTS · DISCUSSION
[128]
The effect of aging of the immune system on vaccination responses
The age-related decline in immunity results not only in increased susceptibility to infection but also reduces the prophylactic efficacy of vaccinations.
[129]
Immunosenescence and human vaccine immune responses
Sep 13, 2019 · The age-related dysregulation and decline of the immune system—collectively termed “immunosenescence”—has been generally associated with an ...
[130]
Factors That Influence the Immune Response to Vaccination
Mar 13, 2019 · In this review, we provide an overview of the plethora of studies that have investigated factors that influence humoral and cellular vaccine responses in ...
[131]
Host genetic factors can impact vaccine immunogenicity and ...
Host genetic factors can impact vaccine immunogenicity and effectiveness ... influence of human genetic factors on vaccine effectiveness is a neglected issue.
[132]
Will Host Genetics Affect the Response to SARS-CoV-2 Vaccines ...
The influence of host genetics on vaccine response occurs if polymorphisms or mutations exist in genes related directly or indirectly to the host immune ...
[133]
Vaccination against rapidly evolving pathogens and the ... - PubMed
Oct 9, 2024 · This Review examines how past exposures shape B cell responses to vaccinations with influenza and SARS-CoV-2.
[134]
Why the evolution of vaccine resistance is less of a concern ... - PNAS
But like all disease interventions targeted at pathogen fitness, drugs and vaccines may drive pathogen evolution that undermines their efficacy, threatening the ...
[135]
Pathogen evolution in a vaccinated world - Oxford Academic
In all three cases, virulence evolution has eroded vaccine efficacy, and hosts infected with these vaccine-breakthough strains are at greater risk of death.
[136]
Host Factors Impact Vaccine Efficacy: Implications for Seasonal and ...
Oct 15, 2019 · Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of ...
[137]
Host factors and vaccine efficacy: Implications for COVID‐19 vaccines
Vaccine efficacy is influenced by several factors including: infectious agent (genetic variation), vaccine factors (type of vaccine, adjuvant, dose and ...
[138]
Vaccine cold chain management and cold storage technology to ...
The selection of cold storage is very important considering the property and efficacy of vaccines are very sensitive to changes in temperature (Hatchett, 2017).
[139]
[PDF] Vaccine Storage and Handling Toolkit | CDC
Mar 29, 2024 · Vaccines exposed to storage temperatures outside the recommended ranges may have reduced potency, creating limited protection and resulting in ...
[140]
Left out in the cold - inequity in infectious disease control due to cold ...
Jan 25, 2025 · The study reported that the HSV-2 vaccine and influenza A virus retained their immunogenicity for 2 months and 3 months respectively at 40 °C, ...
[141]
Factors influencing estimated effectiveness of COVID-19 vaccines in ...
Factors influencing vaccine effectiveness estimates · Pre-existing immunity · Vaccination misclassification · Exposure differences · Testing · Disease risk factor ...
[142]
Host factors and vaccine efficacy: Implications for COVID‐19 vaccines
Nov 29, 2021 · In general, immunosenescence, inflammaging, poor diet, diversity and composition of gut microbiota, and high prevalence of comorbidities are ...
[143]
WHO vaccine reaction rates information sheets
These information sheets include a short summary of the vaccine. They also comprise details of mild and severe adverse reactions (local and systemic) following ...
[144]
Safety Surveillance of Diphtheria and Tetanus Toxoids and Acellular ...
DTaP is reported to have mild local and systemic adverse reactions and less frequent serious adverse events (AEs) compared to DTwP [4].
[145]
Safety of Vaccines Used for Routine Immunization of US Children
Aug 1, 2014 · This study systematically reviewed the literature on the safety of routine vaccines recommended for children in the United States.<|separator|>
[146]
Vaccines Safety in Children and in General Population - Frontiers
In our study, the most common AEFI related to vaccines were fever, injection-site reactions, rash, vomit, and fatigue, i.e., mild and transient untoward medical ...
[147]
Adverse Events Following Measles, Mumps, and Rubella Vaccine in ...
MMR is well tolerated, and most adverse events (AEs) are mild and self-limited (eg, fever, rash, lymphadenopathy, parotitis, transient arthralgias/arthritis).
[148]
Anaphylaxis after vaccination reported to the Vaccine Adverse Event ...
Anaphylaxis after vaccination is a rarely reported event in the United States, with a reported rate of 1.3 cases per 1 million doses administered. The data in ...
[149]
Global burden of vaccine-associated Guillain-Barré syndrome over ...
Oct 19, 2024 · Most vaccines showed significant associations with GBS such as Ad5-vectored COVID-19 vaccines (ROR, 14.88; IC, 3.66), COVID-19 mRNA vaccines ( ...
[150]
Population-Based Incidence of Guillain-Barré Syndrome During ...
Feb 2, 2022 · The pooled incidence rate of GBS was 3.09 per million persons (95% confidence interval [CI]: 2.67 to 3.51) within six weeks of vaccination.
[151]
Chapter 4: Vaccine Safety | Pink Book - CDC
Apr 3, 2024 · Adverse events following immunization can be classified by frequency (common, rare), extent (local, systemic), severity (mild, moderate, severe) ...
[152]
Vaccines and Guillain-Barré syndrome - PubMed
Our review indicates that, with rare exceptions, associations between vaccines and GBS have been only temporal. There is little evidence to support a causal ...
[153]
About the Vaccine Adverse Event Reporting System (VAERS) - CDC
Aug 7, 2024 · While serious adverse events can happen after vaccination, they are rarely caused by the vaccine. NEW! Expanded public access to VAERS data. On ...
[154]
Surveillance for Safety After Immunization: Vaccine Adverse Event ...
Overall, 14.2% of all reports received in VAERS during 1991--2001 described serious adverse events (10) (Table 9). During 1991--2001, reports of deaths ranged ...
[155]
Guide to Interpreting VAERS Data
May 8, 2025 · No proof that the event was caused by the vaccine is required in order for VAERS to accept the report.
[156]
About the Vaccine Safety Datalink (VSD) - CDC
Sep 12, 2025 · Established in 1990, the VSD members monitor the safety of vaccines and conduct studies about rare and serious adverse events following ...
[157]
Vaccine Adverse Event Reporting System (VAERS) Questions ... - FDA
Oct 4, 2024 · VAERS reports generally cannot be used to determine if a vaccine caused or contributed to an adverse event or illness. Some events may occur ...
[158]
The Global Vaccine Safety Initiative (GVSI)
The GVSI was set up to provide WHO and partners with a framework for enhancing vaccine pharmacovigilance. 18 September 2014. The Global Vaccine Safety ...
[159]
Progress in Immunization Safety Monitoring — Worldwide, 2020–2022
Dec 8, 2023 · This report describes 2020–2022 global, regional, and national progress in use of the newly introduced immunization safety monitoring indicator.
[160]
enhancing vaccine pharmacovigilance capacity at country level - PMC
The WHO global vaccine safety resource centre is a website that provides on-site and distance-learning opportunities to public health officials, immunization ...
[161]
Pharmacovigilance - World Health Organization (WHO)
The WHO Pharmacovigilance team strives to ensure safer use of medicines and vaccines throughout the life cycle of the products. We produce reliable, balanced ...
[162]
Vaccine Adverse Event Reporting System (VAERS)
Have you had a reaction following a vaccination? · Report an Adverse Event · Search VAERS Data · Review Resources · Submit Follow-up Information · Helpful Links.VAERS Data · Report an Adverse Event · About VAERS · Seasonal Flu Updates
[163]
The Vaccine Safety Datalink: successes and challenges monitoring ...
The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention(CDC) and 9 health care organizations.
[164]
Serious AEFI - World Health Organization (WHO)
Based on the advice from GACVS to review the causality assessment system, WHO commissioned a group of experts to develop a methodology and tools to assist ...
[165]
The WHO Algorithm for Causality Assessment of Adverse Effects ...
The WHO has proposed a protocol that uses a list of specific questions about vaccine-related adverse events and an algorithm for making a judgement.
[166]
Causality assessment of an adverse event following immunization ...
Apr 16, 2021 · An AEFI causality assessment software was developed, translated to six UN languages and made available online. Recently, the new methodology has been ...
[167]
Causality assessment of adverse events reported to the Vaccine ...
We found that causality could be classified in the majority (97%) of VAERS reports; most were classified unrelated or unlikely to be related to vaccine(s).
[168]
A Causality Assessment Framework for COVID-19 Vaccines and ...
Jul 2, 2024 · Adverse reactions suggest a causal link, whereas AEs do not necessarily indicate a direct result of vaccination. Furthermore, the primary ...
[169]
Aluminum-Adsorbed Vaccines and Chronic Diseases in Childhood
This nationwide cohort study did not find evidence supporting an increased risk for autoimmune, atopic or allergic, or neurodevelopmental disorders
[170]
Vaccine Safety: Examine the Evidence - HealthyChildren.org
Nov 21, 2024 · Research continues to confirm that vaccines are safe and effective—and they protect children and teens from serious diseases.
[171]
How Vaccine Safety Monitoring Works - CDC
Aug 8, 2024 · CDC monitors for a range of side effects after vaccination and acts quickly to notify the public of new findings or, in some cases, to remove a product from ...
[172]
Serious adverse events of special interest following mRNA COVID ...
Sep 22, 2022 · The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % ...<|control11|><|separator|>
[173]
How Does the Federal Government Monitor Vaccine Safety? - KFF
Jul 16, 2025 · This issue brief gives an overview of the main systems used by the federal government to track vaccine safety and adverse events following ...Background · Post-licensure Rapid... · Vaccine Adverse Events...
[174]
How the U.S. Ensures Vaccine Safety | Johns Hopkins
Feb 21, 2025 · Clinical trials, government agencies, and data systems ensure vaccines meet high safety standards.Missing: term | Show results with:term
[175]
The MMR vaccine and autism: Sensation, refutation, retraction ... - NIH
In 1998, Andrew Wakefield and 12 of his colleagues[1] published a case series in the Lancet, which suggested that the measles, mumps, and rubella (MMR) ...
[176]
Lancet retracts 12-year-old article linking autism to MMR vaccines
Feb 2, 2025 · Twelve years after publishing a landmark study that turned tens of thousands of parents around the world against the measles, mumps and rubella (MMR) vaccine
[177]
A timeline of the Wakefield retraction | Nature Medicine
28 February 1998 Gastroenterologist Andrew Wakefield reports in The Lancet that his team has found a “genuinely new syndrome”—a link between the measles, mumps ...
[178]
Vaccines and Autism: A Tale of Shifting Hypotheses - PMC
Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed.
[179]
Do vaccines cause autism? - Autism Speaks
It is possible that the timing of an autism diagnosis or onset of autism symptoms might coincide with the recommended vaccine schedule for children, but this is ...
[180]
Autism and Vaccines - CDC
Dec 30, 2024 · No links have been found between any vaccine ingredients and ASD. Vaccines do not cause autism. Autism spectrum disorder (ASD) is a ...
[181]
Measles, Mumps, Rubella Vaccination and Autism - ACP Journals
The hypothesized link between measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake. This study finds no ...
[182]
The myth of vaccination and autism spectrum - PMC - PubMed Central
Despite the overwhelming data demonstrating that there is no link between vaccines and autism, many parents are hesitant to immunize their children.
[183]
Immunization Safety Review: Vaccines and Autism - NCBI Bookshelf
This eighth report from the committee examines the hypothesis that vaccines, specifically the measles-mumps-rubella (MMR) vaccine and thimerosal-containing ...
[184]
Continuing Increases in Autism Reported to California's ...
Jan 1, 2008 · ContextPrevious analyses of autism client data reported to the California Department of Developmental Services (DDS) have been interpreted ...
[185]
Autism rates up despite removal of mercury from vaccines - CNN.com
A new study published in the January 2008 issue of Archives of General Psychiatry found the prevalence of autism cases in California children continued to ...
[186]
Thimerosal and Vaccines - CDC
Methylmercury is the type of mercury found in certain kinds of fish. At high exposure levels methylmercury can be toxic to people. In the United States, federal ...
[187]
Thimerosal-Containing Vaccines and Autism: A Review of Recent ...
Certain fish contain methylmercury, and ethylmercury is a component of thimerosal used in vaccines. Although these 2 organic forms of mercury are related, they ...<|separator|>
[188]
WHO statement on autism-related issues
Sep 24, 2025 · The World Health Organization (WHO) emphasizes that there is currently no conclusive scientific evidence confirming a possible link between ...
[189]
The Evidence on Vaccines and Autism | Johns Hopkins
Mar 19, 2025 · In 1971, the FDA approved the measles-mumps-rubella (MMR) vaccine, which combined three vaccines that had been approved previously—in 1963, ...
[190]
Immunization Safety Review: Multiple Immunizations and ... - NCBI
A recent survey suggests that a substantial minority of parents (23–25%) believes that getting too many immunizations weakens a child's immune system and that ...
[191]
do multiple vaccines overwhelm or weaken the infant's immune ...
The infant's immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system.
[192]
Summary - The Childhood Immunization Schedule and Safety - NCBI
With the current schedule, children may receive up to 24 immunizations by age 2 years and up to 5 injections in a single visit. Although the number of vaccines ...
[193]
Association Between Estimated Cumulative Vaccine Antigen ...
Mar 6, 2018 · This nested case-control study compares cumulative vaccine antigen exposure through the first 23 months of life among children with vs ...
[194]
Addressing Parents' Concerns: Do Multiple Vaccines Overwhelm or ...
Jan 1, 2002 · This article will provide health care professionals with information about the effect of vaccines on the infant's immune system.
[195]
Immune overload - World Health Organization (WHO)
Jun 7, 2006 · The available evidence reviewed by GACVS does not support the hypothesis that vaccines, as currently used, weaken or harm the immune system.
[196]
Multiple vaccinations and the risk of medically attended fever
This study evaluated rates of medically attended fever after infant vaccination using computerized data from 1991 to 2000 from two large US provider groups.Abstract · Introduction · Study Population
[197]
Safety and efficacy of combination vaccines - NIH
In the study by Schmitt et al, no difference was found in subjects achieving protective concentrations of antibodies against diphtheria, tetanus, hepatitis B, ...
[198]
Multiple Vaccines at Once - CDC
Dec 20, 2024 · When a baby is born, his or her immune system is ready to respond to the many antigens in the environment and the selected antigens in vaccines.
[199]
Exploring the interplay between vaccines and immune system ...
Mar 5, 2024 · Research out of St. Jude investigates how the immune system in infants responds to a routine vaccine panel at two months.
[200]
Nuremberg Code - UNC Research
—“Permissible Medical Experiments.” Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Nuremberg October 1946 – ...
[201]
Do vaccine mandates impair the voluntariness of informed consent?
An ethical and legal obligation generally exists for informed consent to be obtained prior to the administration of medical interventions.
[202]
Full article: Is informed consent correctly obtained for vaccinations?
Informed consent is an integral tenet of medical ethics. However, the United States lacks a standardized consent process for immunizations, with states and ...
[203]
Jacobson v. Massachusetts | 197 U.S. 11 (1905)
This case involves the validity, under the Constitution of the United States, of certain provisions in the statutes of Massachusetts relating to vaccination.Missing: ethics | Show results with:ethics
[204]
Immunization Mandates, Vaccination Coverage, and Exemption ...
Permission of religious and philosophical exemptions was associated with 2.3% and 1.9% decreases in MMR and DTaP coverage, respectively, and a 1.5% increase in ...Table 2 · Laws And Vaccination... · Vaccination Coverage Law...
[205]
Vaccine Refusal, Mandatory Immunization, and the Risks of Vaccine ...
Multiple studies have shown an increase in the local risk of vaccine-preventable diseases when there is geographic aggregation of persons refusing vaccination.
[206]
The Case against compulsory vaccination - Journal of Medical Ethics
Arguments for mandatory or compulsory vaccination must justify the coercive infringement of bodily integrity via the injection of chemicals that permanently ...
[207]
Integrating civil liberty and the ethical principle of autonomy in ... - NIH
Vaccination raises ethical dilemmas between the autonomy of an individual who has the right to make decisions about their own body which includes the refusal or ...
[208]
Vaccination Coverage and Exemptions among Kindergartners - CDC
Jul 31, 2025 · During the 2024-2025 school year, exemptions from one or more vaccines among kindergartners in the U.S. increased to 3.6% from 3.3% the year ...
[209]
Coverage with Selected Vaccines and Exemption Rates Among ...
Oct 17, 2024 · Coverage dropped below 93% for the 2023–24 school year, ranging from 92.3% for DTaP to 92.7% for MMR. Exemptions increased to 3.3%, compared with those during ...
[210]
Ethics and Effectiveness of US COVID-19 Vaccine Mandates ... - NIH
Results: The review showed vaccine mandates are ethical and effective if autonomy-centered alternatives like soft mandates are first exhausted.
[211]
Ethical Issues in Mandating COVID-19 Vaccination for Health Care ...
At least one court has upheld a hospital's legal right to impose a COVID-19 vaccine mandate. Here we discuss whether vaccine mandates for HCP should be adopted.
[212]
The unintended consequences of COVID-19 vaccine policy
May 26, 2022 · We argue that current mandatory vaccine policies are scientifically questionable and are likely to cause more societal harm than good.
[213]
Mandating COVID-19 Vaccines | Law and Medicine - JAMA Network
Dec 29, 2020 · In this Viewpoint, we examine whether vaccine mandates would be lawful and ethical and whether they could boost vaccine uptake.
[214]
[PDF] FDA at a Glance
The remaining 45 percent, or $2.7 billion, is paid for by industry user fees. • The FDA budget is equivalent to $9.95 per. American per year. • The FDA budget ...
[215]
Why is the FDA Funded in Part by the Companies It Regulates?
May 21, 2021 · Of the FDA's total US$5.9 billion budget, 45% comes from user fees, but 65% of the funding for human drug regulatory activities are derived ...
[216]
Prescription Drug User Fee Amendments - FDA
Sep 30, 2025 · The Prescription Drug User Fee Act (PDUFA) was created by Congress in 1992 and authorizes FDA to collect user fees from persons that submit certain human drug ...
[217]
Despite RFK Jr claims, conflicts of interest among federal vaccine ...
Aug 19, 2025 · Despite RFK Jr claims, conflicts of interest among federal vaccine advisers very low, study finds ... approved vaccines, was the culmination of ...
[218]
Conflicts of Interest on CDC Vaccine Panel Were at Historic Lows ...
Aug 18, 2025 · Reported conflicts of interest among vaccine advisors dropped considerably over the last 25 years · Very few advisors in the past decade reported ...
[219]
Pharmaceuticals/Health Products Lobbying Profile - OpenSecrets
Annual Lobbying on Pharmaceuticals/Health Products ; Abbott Laboratories, $2,603,507 ; Otsuka Pharmaceutical, $2,520,000 ; Biogen, $2,400,000 ; GSK plc, $2,310,000.
[220]
Pharmaceutical Companies' Role in State Vaccination Policymaking
Most stakeholders found lobbying by vaccine manufacturers acceptable in principle, but perceived that Merck had acted too aggressively and nontransparently in ...
[221]
The interdependent influence of lobbying and intellectual capital on ...
In the first quarter of 2020, just after the COVID-19 outbreak, big pharma firms and other health organizations allegedly spent nearly $250 million on lobbying ...
[222]
Pharmaceutical Industry on Pace for Record Lobbying Spending
Aug 29, 2025 · Pfizer, Merck, Eli Lilly and other drug giants are spending record amounts on lobbying as they fight the Trump administration on vaccine ...
[223]
Transparency of COVID-19 vaccine trials: decisions without data
There is inadequate availability of COVID-19 vaccine trial documents and data; individual participant data will not be available for months, perhaps years, for ...
[224]
[PDF] Corruption in vaccine research and clinical trials
In one 2017 study, an estimated 44% of 150 clinical trials contained at least some flawed data such as flawed statistics, incorrect calculations or duplicated ...
[225]
FDA Closing the Clinical Trial Reporting Gap for Research Integrity
Sep 26, 2025 · The FDA is committed to ensuring data transparency by promoting timely registration and reporting of results information to ClinicalTrials.gov ...Missing: vaccine | Show results with:vaccine
[226]
Joint Statement on transparency and data integrity
Lack of public access to negative trials has been identified as a source of bias, which weakens the conclusions of systematic reviews and provides a false sense ...
[227]
COVID vaccine confidence requires radical transparency - Nature
Sep 29, 2020 · Public trust in a potential vaccine is under threat. Drug companies and their academic partners must disclose protocols and results data.
[228]
Costs of Interventions to Increase Vaccination Coverage Among ...
Across all interventions and age groups, the cost per child ranged from $0.10 to $537.38, and the incremental cost per vaccinated child ranged from $6.52 to ...
[229]
Health and Economic Benefits of Routine Childhood Immunizations ...
Aug 8, 2024 · This report describes health and economic benefits from routine childhood vaccines among children born during 1994–2023.<|separator|>
[230]
Systematic Review and Meta-Analysis of Cost-effectiveness of ...
Rotavirus vaccine would be cost-effective to introduce in LICs and LMICs. These findings could aid decision makers and provide evidence for introduction of ...Missing: peer- | Show results with:peer-
[231]
Estimating the impact of vaccination on reducing COVID-19 burden ...
Vaccination in the US saved US$895.4 (95% CrI = US$611.9-1199.2) billion in direct health care costs and $26.9 (95% CrI = US$19.5-34.2) billion in indirect cost ...
[232]
Economic benefits and costs associated with target vaccinations
Conclusions: In general, as a therapeutic class, vaccines are extremely cost-effective agents. In addition, they are one of the few public health interventions ...<|separator|>
[233]
Making vaccine refusal less of a free ride - PMC - NIH
Herd immunity against vaccine-preventable diseases is a public good because it is both non-excludable (meaning that there is no way to exclude people from using ...
[234]
Herd Immunity and Positive Externalities - J.V. Bruni and Company
Herd immunity is achieved when 60% or more of a population is immune. Vaccination provides a positive externality, as immunized people protect others.
[235]
The societal cost of vaccine refusal: A modelling study using ...
Jun 23, 2023 · Our findings demonstrate that even low levels of vaccine refusal can have a substantial and measurable societal burden on the population.
[236]
Return On Investment From Immunization Against 10 Pathogens In ...
Aug 3, 2020 · ROI reflects the average economic benefit realized per dollar invested in immunization programs. Using the cost-of-illness approach to estimate ...
[237]
Vaccines have a high return on investment, every $1 spent ... - VoICE
Vaccines have a high return on investment, every $1 spent on vaccine programs returns up to $44. A recent study estimated that, during the decade from 2011- ...
[238]
Herd immunity, vaccination and moral obligation - PMC - NIH
Jun 5, 2023 · In the case of endemic diseases like COVID-19, herd immunity is best understood as a dynamic equilibrium between the pathogen and population ...Missing: mechanism | Show results with:mechanism
[239]
Data-related challenges in cost-effectiveness analyses of vaccines
In this paper we describe selected challenges to conducting CEAs for vaccination strategies, with a focus on issues related to epidemiological inputs and ...
[240]
The herd-immunity threshold must be updated for multi-vaccine ...
Nov 26, 2021 · However, that classic threshold is defined only for a single vaccine and may be invalid and biased when we have multi-vaccine strategies for a ...
[241]
Herd Immunity Effects in Cost-Effectiveness Analyses among Low
Jan 10, 2022 · This study investigated how the inclusion of HI in CEAs may influence the reported value of immunizations in low- and middle-income countries (LMICs)
[242]
Impact of vaccine herd-protection effects in cost-effectiveness ...
In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of ...<|control11|><|separator|>
[243]
Methodological Challenges to Economic Evaluations of Vaccines
This paper discusses the challenges to standard economic evaluation of vaccines that have been raised, the extent to which proposed methodological changes may ...
[244]
Efficacy, immunogenicity and safety of COVID-19 vaccines in older ...
COVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease.
[245]
Disparities in response to mRNA SARS-CoV-2 vaccines according ...
Age significantly impacts the immune response to COVID-19 vaccines, with younger individuals showing higher antibody levels and better overall vaccine efficacy.
[246]
Effect of age at vaccination on the measles vaccine effectiveness ...
Mar 29, 2020 · Earlier age at MCV1 decreases measles protection and immunogenicity after one dose and might still have an impact on vaccine failures after two doses of ...
[247]
Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 ...
May 27, 2021 · The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly ...<|separator|>
[248]
Sex Difference in Immune Response to Vaccination: A Participant ...
Using a participant-level meta-analysis of completed randomized trials, we observed a statistically significant sex difference in humoral immune response to ...
[249]
Sex Differences in Immunity: Implications for the Development of ...
Findings from clinical trials have underlined that sex might have a crucial influence on the vaccine response. A higher magnitude of immune responses in adult ...
[250]
Sex differences in adverse events following seasonal influenza ...
This meta-analysis suggested a higher risk of solicited reactions following influenza vaccines for females compared with males, irrespective of age and vaccine ...
[251]
Sex Differences in the Immunogenicity and Efficacy of Seasonal ...
Our results suggest a higher immunogenicity and VE in females compared to males in older adults. These differences in immunogenicity and VE support the ...
[252]
Vaccination for the Prevention of Infection among ... - NIH
May 18, 2022 · This review of 54 systematic reviews demonstrated three vaccine seroconversion response categories among immunocompromised patients.
[253]
Vaccination of Adults With Cancer: ASCO Guideline
Mar 18, 2024 · ACIP recommends that immunocompromised patients receive a higher antigen dose as shown in Table 2.
[254]
Vaccination in the Era of Immunosuppression - PMC - NIH
Sep 1, 2023 · Ideally, immunosuppressed AIIRD patients should receive vaccinations at least two weeks before commencing immunosuppressive treatment. However, ...
[255]
Vaccines for Moderately to Severely Immunocompromised People
Jun 11, 2025 · CDC recommends an updated COVID-19 vaccine for people 6 months and older who are moderately or severely immunocompromised. Vaccine ...
[256]
HLA Class II Genes HLA-DRB1, HLA-DPB1, and HLA-DQB1 Are ...
Mar 7, 2019 · To date, many studies have reported that HLA class II genes are associated with the vaccine antibody response (17, 26–30). In 1999, McDermott et ...
[257]
Genetic determinants of IgG antibody response to COVID-19 ...
Jan 4, 2024 · Notably, host genetic factors, along with variables such as sex, age, and ethnicity, have been identified as significant contributors to ...
[258]
Gene Polymorphism in Toll-like Receptor 4: Effect on Antibody ...
Mar 1, 2012 · An association between polymorphism in the TLR4 promoter and the antibody response to the whole-cell pertussis vaccine has been noticed [11, 13] ...
[259]
The polymorphisms of TNF-α related-gene and antibody production ...
In this study, TNF-α related gene (GG) significantly influenced the formation of the antiSARS-CoV-2 spike protein IgG antibody level (p = 0.005) in our sample.
[260]
Genetic variation in the response to vaccination - PubMed
This review focuses on genetic factors that determine the variable response to vaccination. The highly polymorphic human leukocyte antigen system,
[261]
Impact of host genetic polymorphisms on vaccine induced antibody ...
Many host- and vaccine-specific factors modulate an antibody response. Host genetic polymorphisms, in particular, modulate the immune response in multiple ...
[262]
Mayo Clinic Discovers African-Americans Respond Better to Rubella ...
Feb 26, 2014 · Somali Americans develop twice the antibody response to rubella from the current vaccine compared to Caucasians in a new Mayo Clinic study.
[263]
Ethnic Differences in Immune Responses to Hepatitis B Vaccine
Children in three of the four aboriginal villages had significantly lower titers of antibody against hepatitis B surface antigen (anti-HBs) than did children in ...Missing: immunogenicity | Show results with:immunogenicity
[264]
Human leukocyte antigen variants associate with BNT162b2 mRNA ...
Apr 4, 2024 · These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies ...
[265]
Covid-19 vaccine trials: Ethnic diversity and immunogenicity
Furthermore the paucity of ethnic diversity in vaccine trials means efficacy may differ between countries, resulting in health disparities. This commentary ...
[266]
Covid-19 vaccine trials: Ethnic diversity and immunogenicity - PMC
As part of the study sub-analysis 36.5% of participants were from ethnic minority backgrounds (20% Hispanic/Latino, 9.7% African-American, 4.7% Asian, and <3% ...
[267]
About the Vaccines for Children (VFC) Program - CDC
Jun 26, 2024 · The Vaccines for Children (VFC) Program provides vaccines to children whose parents or guardians may not be able to afford them.Information for Parents · Information for Providers · How Public Programs and...
[268]
Vaccines for Children Program | Georgia Department of Public Health
Apr 16, 2025 · The Vaccines for Children (VFC) Program is intended to help raise childhood immunization levels in the United States, especially infants and young children.
[269]
https://www.immunize.org/official-guidance/state-policies/requirements/
[270]
https://www.immunize.org/official-guidance/state-policies/exemptions/
[271]
Vaccine Policy Remains a Topic of Interest for State Legislatures
May 9, 2025 · In the first three months of 2025, more than 370 vaccine-related bills were introduced across 44 states and Puerto Rico. About 42% of introduced ...
[272]
After Florida announced a plan to ban vaccine mandates, what's ...
Sep 5, 2025 · Florida officials announced this week that the state will work to phase out all childhood vaccine mandates, becoming the first in the U.S. ...
[273]
Jacobson v Massachusetts at 100 Years: Police Power and Civil ...
In affirming Massachusetts' compulsory vaccination law, the Court established a floor of constitutional protections that consists of 4 standards: necessity, ...
[274]
Immunization Programs - NCBI - NIH
The Expanded Programme on Immunization (EPI), with recommended guidelines established by the World Health Organization, is a major international effort to ...
[275]
Immunization coverage - World Health Organization (WHO)
Jul 15, 2025 · The proportion of children receiving a first dose of measles vaccine was 84% in 2024, still not at the 2019 level of 86%.
[276]
Vaccines and immunization - World Health Organization (WHO)
Vaccination is a simple, safe, and effective way of protecting people against harmful diseases, before they come into contact with them.Missing: peer- | Show results with:peer-
[277]
Global immunization efforts have saved at least 154 million lives ...
Nearly 94 million of the estimated 154 million lives saved since 1974, were a result of protection by measles vaccines.
[278]
Prevalence, predictors and reasons for COVID-19 vaccine hesitancy
Concerns regarding potential side effects is the most frequent reason for vaccine hesitancy. •. Lack of trust is consistently the strongest predictor of extreme ...Missing: causes empirical
[279]
The Problem Isn't Trust in Vaccines, It's That People Don't Know ...
Aug 19, 2025 · Public confidence in the safety of vaccines for measles, mumps, and rubella (MMR) is highest at 83%, next highest for flu (74%), then falls off ...
[280]
The 2025 United States Measles Crisis: When Vaccine Hesitancy ...
Jul 17, 2025 · This narrative review examines how declining vaccine uptake and growing vaccine hesitancy created pockets of susceptibility that enabled the ...Missing: empirical | Show results with:empirical
[281]
New poll reflects broad American distrust in health agencies and ...
Oct 17, 2025 · The share who "strongly agree" has fallen from 51% to 39% over that period, "likely reflecting both shifts in trust toward the CDC as well as in ...
[282]
New data indicates declining confidence in childhood vaccines of up ...
New UNICEF report shows 67 million children missed out on one or more vaccinations over three years due to service disruption caused by strained health systems ...Missing: empirical | Show results with:empirical
[283]
Determinants of vaccine hesitancy among healthcare workers in an ...
Aug 28, 2025 · A total of 2079 healthcare workers (HCWs) responded to an anonymous survey on vaccine hesitancy conducted between December 2022 and October ...Missing: empirical | Show results with:empirical<|separator|>
[284]
The unintended consequences of COVID-19 vaccine policy - NIH
Our analysis strongly suggests that mandatory COVID-19 vaccine policies have had damaging effects on public trust, vaccine confidence, political polarization, ...
[285]
[PDF] The negative impacts of Covid vaccine mandates in the United ...
Jul 26, 2023 · “Our analysis strongly suggests that mandatory COVID-19 vaccine policies have had damaging effects on public trust, vaccine confidence, ...
[286]
Transparent communication about negative features of COVID-19 ...
While transparent disclosing of negative vaccine information may hurt in the short term, transparency has key long-term benefits by sustaining trust, which is a ...
[287]
Effective Approaches to Combat Vaccine Hesitancy - PMC - NIH
Strong community engagement and the use of vaccine champions are valuable strategies to address vaccine hesitancy, alongside communication campaigns and ...
[288]
Vaccination and Immunization Statistics - UNICEF DATA
Jul 14, 2025 · In 2024, global coverage of the third dose of diphtheria-tetanus-pertussis (DTP3) vaccine – often used as a marker of how well countries are ...
[289]
Global childhood vaccination coverage holds steady, yet over 14 ...
Jul 15, 2025 · An estimated 2 million more children were reached in 2024, but the overall coverage rate is far below the 95% needed in every community to ...
[290]
Real Barriers to Vaccine Equity: Infrastructure & Distribution
May 5, 2022 · Many struggle with a lack of infrastructure and funding to facilitate widescale distribution. Without adequate distribution systems, countries ...Missing: immunization | Show results with:immunization
[291]
Global Funding Surge to Expand Childhood Immunization Access in ...
May 9, 2025 · Despite the major influx of funding, critical obstacles remain. Delivery delays, supply chain breakdowns, vaccine hesitancy, and geographic ...Missing: barriers | Show results with:barriers
[292]
US Stops Funding for Gavi Global Vaccine Program, Sparking ...
Jul 2, 2025 · The United States will stop sending money to Gavi, a global group that helps vaccinate children in low-income countries.Missing: challenges | Show results with:challenges
[293]
Capacity Building for Vaccine Manufacturing Across Developing ...
Approved vaccines prevent 2 to 3 million deaths per year. There is a lack of equitable access to vaccines in the low- and middle-income developing nations.
[294]
Overcoming Barriers: Financing and Service Delivery for ... - HITAP
Feb 28, 2025 · Additionally, a shortage of trained healthcare professionals and funding constraints further hinder vaccination efforts, with fragile states ...
[295]
Barriers to child vaccination: The role of international sanctions
This study empirically examines the impact of international sanctions on child immunization rates in developing countries.
[296]
2024 global immunisation coverage estimates
Jul 15, 2025 · In 2024, 70% of lower-income countries maintained or improved coverage with three doses of the diphtheria, tetanus and pertussis-containing ...
[297]
Challenges to sustainable immunization systems in Gavi ... - NIH
Middle Income Countries (MICs) losing support from Gavi, the Vaccine Alliance, require special attention to achieve Global Vaccine Action Plan (GVAP) targets.
[298]
Immunization Access and Coverage in Middle-Income Countries
Jan 27, 2025 · Gaps in decision-making, vaccine demand, effective financing, and access to sustainable and affordable vaccine supply, limited program capacity, ...