BACKGROUND:Although meningococcal serogroup B (MenB) causes most invasive meningococcal disease (IMD) cases in United States (US) infants, MenB vaccination is not currently approved for this age group. This study sought to better understand US healthcare providers' (HCPs') views regarding IMD and a potential MenB vaccine for children ≤18 months old. RESEARCH DESIGN AND METHODS:An online survey was conducted in November 2024 among US board-certified HCPs who provided care to children ≤18 months old. Responses were analyzed descriptively. RESULTS:Among N = 506 HCPs, 97.8% responded that, if the Advisory Committee on Immunization Practices (ACIP) were to recommend MenB vaccination for children ≤18 months old, it should be recommended for all children in this age group (52.6%) or those at increased risk for IMD (45.3%). Less than one-fifth (17.6%) of HCPs correctly identified the ACIP MenB vaccination recommendation for children ≤18 months old; 84.4% indicated interest in learning more about a potential MenB vaccine if ACIP-recommended for this population. When considering recommending potential MenB vaccination, 68.6% of HCPs anticipated encountering vaccine hesitancy among parents/caregivers. CONCLUSIONS:Most HCPs viewed infant MenB vaccination favorably but demonstrated knowledge gaps regarding IMD epidemiology and vaccine recommendations, underscoring the need for targeted education to optimize future IMD prevention.
INTRODUCTION:Routine meningococcal vaccination campaigns have substantially reduced the burden of invasive meningococcal disease in pediatric individuals, leading to relative increases in burden in older age groups. There is a need for safe, effective meningococcal vaccines that can be used across broad age ranges. MenACYW-TT, a quadrivalent tetanus-toxoid-conjugate meningococcal vaccine indicated for individuals aged ≥6 weeks, is one such option. AREAS COVERED:This narrative review summarizes safety data from industry-sponsored pre- and post-licensure clinical trials of MenACYW-TT, including head-to-head studies with active comparators and coadministration studies with routine pediatric vaccines. EXPERT OPINION:In >30 trials involving >17,000 participants, MenACYW-TT had a consistent safety profile across all age groups, from infants to older adults. The most frequent side effects were generally mild or moderate and transient; vaccine-related serious adverse events were rare (<0.1%). The safety of MenACYW-TT was comparable to that of other quadrivalent meningococcal conjugate vaccines. Coadministration did not materially affect the safety of MenACYW-TT or routine pediatric vaccines. Immunization remains an essential preventive strategy against the potentially life-threatening and life-altering consequences of invasive meningococcal disease. The favorable benefit-risk profile of MenACYW-TT reinforces the safety of licensed vaccines and can help to counter vaccine hesitancy.
Introduction The paradigm of trained immunity (TI), a de facto innate immune memory mediated by metabolic and epigenetic reprogramming of innate leukocytes, has expanded the conceptual framework for rational vaccine adjuvant design. Moving beyond conventional empiricism, TI offers a mechanistic basis that may enhance protection against certain heterologous pathogens, particularly in specific conditions.Areas covered This review provides a comprehensive analysis of next-generation adjuvants engineered to induce TI. We outline the core mechanistic foundations encompassing the PI3K/Akt/mTOR/HIF1α-driven immunometabolic switch and ensuing chromatin rewiring, categorize emerging adjuvant strategies from natural TI inducers to synthetic pattern-recognition receptor agonists, direct metabolic-epigenetic modulators, and self-adjuvanting antigens, examine the enabling role of nanotechnology in achieving spatiotemporal control, and discuss translational roadmaps, safety considerations, and pivotal challenges.Expert opinion TI-inducing adjuvants provide a mechanistic basis for bridging innate and adaptive immunity and represent a promising direction for next-generation vaccine development. Realizing their full potential will require resolving critical challenges in precision-tunability, host heterogeneity, and durability of the trained state, alongside defining validated correlates of protection. The convergence of systems immunology and advanced delivery platforms might accelerate the transition from concept to clinical vaccines, and contribute to the improved preparedness against infectious and noninfectious diseases.
Introduction Influenza A virus poses ongoing global health and economic challenges due to its antigenic variability and pandemic potential. Current seasonal vaccines targeting the variable hemagglutinin (HA) provide limited and strain-specific protection. The conserved Matrix 2 Ectodomain (M2e) offers a promising universal vaccine target, eliciting protection by targeting infected cells rather than neutralizing virions. However, the mechanism underlying protection mediated by this simple antigen is complex, and no M2e-based vaccine has been licensed yet.Area Covered Precise M2e-vaccine optimization is needed. This review provides in-depth description of M2e established knowledge, as well as comparative studies using M2e-based vaccines. From this, the ‘ideal archetype’ of a universal vaccine including M2e will be defined. Finally, a review of the current preclinical nanoparticle based M2e vaccine will be provided, described, and analyzed.Expert opinion Optimizing antigen presentation, evaluating Fc-mediated effector functions with standardized assays, and integrating M2e into multivalent nanoparticle platforms targeting complementary conserved antigens are likely to be key steps toward achieving broad, durable, and clinically translatable protection.
INTRODUCTION:We reviewed evidence on whether vaccinated individuals can transmit measles and conducted a meta-analysis to understand transmission characteristics. METHODS:We searched and extracted data from peer-reviewed and gray literature and included studies reporting measles transmission events from vaccinated individuals. We meta-analyzed the data to calculate the median number of transmissions from vaccinated cases by measles burden, number of doses, and time since first and last dose. RESULTS:We identified 11,911 peer-reviewed and 22 gray literature records and included 33 articles in our review. Seventy individuals who had received 1 or more doses of measles-containing vaccine transmitted measles virus, resulting in 237 secondary cases. Vaccinated transmitters in eliminated areas were older (median age of 19 years (IQR: 3, 21)) than those in non-eliminated areas (median age 16 years; IQR 13, 18) (p = 0.12). Additionally, 91% (30/33) of studies provided data on subsequent transmission generations, leading to 812 measles cases traced back to vaccinated individuals, with a median of 4 (IQR: 1, 10) cases per vaccinated transmitter. CONCLUSION:Measles transmissions from vaccinated cases, although relatively uncommon, must be considered in public health investigations, as such transmissions can contribute to outbreaks.
BACKGROUND:Medicaid beneficiaries typically have low vaccination rates, in part due to limited access. Pharmacies provide easy-to-access locations for vaccination. RESEARCH DESIGN AND METHODS:This was a retrospective analysis of trends in pharmacy-based vaccination by age and race or ethnicity among Medicaid recipients aged ≥9 from 1 January 2018 (before the COVID-19 pandemic) to 31 December 2023. The percentage of all vaccinations administered at pharmacies and the overall percentage change in vaccination rates were determined. RESULTS:With some exceptions, overall routine and seasonal vaccination rates remained lower in 2023 than in 2018-2019. This was observed for human papillomavirus (HPV), influenza, and tetanus-containing (Tdap/Td) vaccines in adolescents and for hepatitis A, influenza, meningococcal, pneumococcal, and Tdap/Td vaccines in various adult age groups. The percentage of routine and seasonal vaccinations administered at pharmacies increased over the study period among adults, with increases of 5.2-17.5 percentage points for hepatitis A, hepatitis B, HPV, meningococcal, pneumococcal, and tetanus-containing vaccines among those aged 19-49. Across age groups, pharmacy-based vaccination was most frequent in White enrollees, followed by Black and then Hispanic enrollees, with smaller differentials in adults aged ≥65. CONCLUSIONS:Generally overall vaccine administration rates declined in Medicaid beneficiaries; however, the proportion administered at pharmacies increased.
BACKGROUND:Respiratory syncytial virus (RSV) can cause serious disease in older adults (OAs), particularly those with comorbidities. It is a leading cause of acute respiratory illness and lower respiratory tract infections in adults ≥60 years. Its impact on morbidity, mortality, and healthcare systems is becoming evident. Questions about the burden of disease (BoD) are raised due to underdiagnosis and the similarity with other respiratory illnesses. First opportunities for prevention came in 2023 and 2024, with vaccines approved for ≥60 years, expanding eligibility to additional age groups. RESEARCH DESIGN AND METHODS:A modified Delphi approach through a questionnaire survey and virtual consensus workshop with 27 experts in respiratory and infectious diseases from 12 emerging market countries was done to reach consensus on diagnosis, prevention, and treatment of RSV in OAs. RESULTS:The panel recommends the introduction of a universal vaccination program for all adults aged ≥70 years, and vaccination for all adults aged ≥60 years with comorbidities. The need for increased awareness, better testing, and national and international guidelines was also agreed. CONCLUSION:The agreements highlight that RSV vaccination for OAs should be prioritized. Educating clinicians and patients, improving surveillance, and integrating RSV vaccination into health policies are key to reducing BoD in OAs.
Introduction Smallpox, eradicated globally in 1980, remains a major biodefense concern due to retained Variola virus stocks and the absence of population immunity following cessation of routine vaccination. Monkeypox virus (MPXV), a related orthopoxvirus, has reemerged as a global public health threat, with major outbreaks in 2022 and renewed spread from 2024 onward.Areas covered This review evaluates ACAM2000®, a second-generation live smallpox vaccine, summarizing its development, immunogenicity, efficacy, safety, regulatory status, and potential role in mpox prevention.Expert opinion ACAM2000 remains a critical medical countermeasure for smallpox preparedness and a valuable, though selective, tool for mpox prevention. Its high immunogenicity, rapid protection, and broad orthopoxvirus coverage must be balanced against a well-characterized safety risk profile.
Introduction Streptococcus pneumoniae asymptomatically colonizes the nasopharynx but can also cause mucosal infections or invasive pneumococcal disease. Despite the significant positive impact of pneumococcal conjugate vaccines, the burden of pneumococcal disease persists, reflecting the inherent limitations of a strategy that elicits serotype-dependent humoral immunity against a pathogen with > 100 known serotypes.Areas covered Animal model data suggest that in addition to anti-capsular antibodies, CD4+ T-cell responses (including Th1 and Th17) and CD8+ T cells may also contribute to protection against pneumococcal colonization and disease. However, the contribution of cellular immune responses against S. pneumoniae in humans has not been fully elucidated, with human challenge models suggesting a potential role for CD8+ T cells, CD4+ Th17 cells, and tissue-resident memory T cells in protection. We summarize here the evidence on cellular immune responses elicited by exposure to S. pneumoniae and provide an overview of the cellular immune responses induced by candidate pneumococcal vaccines (whole-cell vaccines, protein-based vaccines, and vaccines using MAPS technology).Expert opinion Improving protection against S. pneumoniae will require future pneumococcal vaccines to induce a broad, multipronged immune response. This strategy implies identifying new immunological benchmarks beyond capsular antibodies. Therefore, defining protective cellular responses represents a critical research priority.
BACKGROUND:Influenza vaccination is an evidence-based intervention for older adults. However, vaccination coverage remains low and uneven in China, indicating persistent evidence-practice gap. Although older adults often express willingness to be vaccinated, uptake often varies across different implementation contexts. Therefore, we explored how implementation determinants govern vaccination uptake. RESEARCH DESIGN AND METHODS:We conducted a comparative qualitative study using semi-structured interviews with older adults in Beijing and Guizhou. The interview guide was developed using the Consolidated Framework for Implementation Research (CFIR), and data were analyzed thematically and mapped to CFIR domains to compare determinants across sites. RESULTS:Seventy-six participants were enrolled, including 40 from Beijing and 36 from Guizhou. Across both locations, many participants expressed willingness to be vaccinated but did not always follow through, reflecting an intention-uptake gap. Determinants in the Outer Setting and Process/Inner Setting domains were most significant in shaping vaccination uptake. Trusted communication and institutional triggers, including clinician recommendations and community reminders, facilitated vaccination uptake in Beijing. These cues were less available in Guizhou, where fragmented information contributed to delays and non-uptake. CONCLUSIONS:Implementation strategies should make influenza vaccination a more routine and system-supported component of healthy aging services. This requires stronger service delivery systems and standardized communication.
BACKGROUND:We estimated the XBB.1.5 vaccine effectiveness (VE) against COVID-19 hospitalization and death in Belgium, Denmark, Italy, Portugal, Spain (Navarre), and Sweden following the 2023-24 fall vaccination campaign among immunocompromised persons (ICPs). RESEARCH DESIGN AND METHODS:We conducted a multi-country retrospective cohort study using electronic health records. Study sites identified ICPs aged ≥18 years through a common set of immunocompromising conditions and follow-up started the first day of the 2023 vaccination campaign until 12 months later. VE was calculated by time since vaccination (14-59, 60-119, 120-179, 180-365 days after vaccination) for ICPs by pooling study site level confounder adjusted hazard ratios (aHR) of vaccination, estimated with Cox proportional hazards regression models, using a random effect meta-analysis with VE = 100 × (1-pooled aHR). RESULTS:The XBB.1.5 VE was 52% (95% confidence interval (CI): 41 to 60) and 75% (95%CI: 60 to 84) against hospitalization and death, respectively, 14-59 days after vaccination, and VE decreased with time since vaccination with no remaining protection at 180-365 days after vaccination. CONCLUSION:Adapted XBB.1.5 vaccine provided moderate protection within 120 days after vaccination against severe COVID-19 outcomes among ICPs aged ≥18 years during a period with BA.2.86/JN.1 replacing the XBB.1.5 variant.
Introduction Community-acquired pneumonia (CAP) remains a significant cause of adult morbidity and mortality. Respiratory syncytial virus (RSV) contributes meaningfully to adult CAP, particularly in older adults and those with chronic cardiopulmonary disease, yet is frequently underdiagnosed because clinical features overlap with other respiratory infections and routine testing is limited.Areas covered This review summarizes key virological and immunological characteristics of RSV, highlights diagnostic challenges in adults, and discusses clinical consequences beyond respiratory illness, including cardiovascular complications, severe in-hospital outcomes, and secondary bacterial infection with antibiotic exposure. Using Korean and international data, we emphasize the value of multi-specimen molecular testing to improve detection and discuss the implications for antimicrobial stewardship in CAP management. We also provide an overview of vaccine efficacy in phase 3 trials and early real-world effectiveness in older adults.Expert opinion Reducing the adult RSV burden will require a feasible diagnostic pathway during periods of RSV circulation, strengthened surveillance that captures clinically meaningful outcomes, and targeted vaccination of high-risk populations. Ongoing post-authorization evaluation and research in immunocompromised and other high-risk groups are needed to optimize vaccination strategies and inform next-generation prevention.
Background Pneumococcal disease, respiratory syncytial virus (RSV), influenza, and COVID-19 place a significant burden on France’s population health, health system, and economy. Older adults and adults in clinical risk groups are recommended to receive vaccination against these illnesses, although RSV is not reimbursed.Research design and methods A benefit–cost analysis was conducted to assess the societal return on investment from adult vaccination by estimating benefit–cost ratios (BCRs) and net benefits (NBs). Health outcomes were monetized using established methods. Program costs included all direct vaccination-related expenditures. Scenario and sensitivity analyses assessed alternative program specifications and tested the robustness of the model.Results France’s age-based respiratory immunization programs generate a BCR of €2.0 to €8.7 per €1 spent over the lifetime, depending on mortality risk reduction monetization. This corresponds to NBs of €9.7 to €72.6 billion. Introducing adult RSV vaccination with a similar uptake to that in the US could increase NBs by approximately 6%–7% compared to the status quo. Achieving aspirational coverage targets across all programs would increase NBs by 138%–175%.Conclusions France’s adult respiratory vaccination programs generate positive socioeconomic returns. Including adult RSV vaccination and increasing vaccination uptake would further increase their societal benefits. Realizing these gains requires adequate public investment.
BACKGROUND:In Sweden, older adults and adults in clinical risk groups are recommended vaccination against pneumococcal disease, respiratory syncytial virus, influenza, and COVID-19. However, vaccine uptake remains inadequate. This study estimates the socioeconomic benefits of these immunization programs under current coverage compared to aspirational scenarios, assessing the value foregone due to suboptimal uptake. METHODS:We conducted a benefit-cost analysis from a societal perspective applying life table-based disease models to estimate benefit-cost ratios (BCRs) and net benefits (NBs). Health impacts were monetized through the value-of-a-statistical-life and cost-of-illness approaches. Costs comprised vaccination program expenses. Scenario and sensitivity analyses explore coverage and program eligibility. RESULTS:Vaccination programs in older adults generated BCRs of 3:1 and NBs of SEK 54.4 billion over a lifetime (VSLY). When risk groups were included to model current strategies in Sweden, NBs increased to SEK 59.7 billion. Reaching aspirational coverage targets increased NBs by 18%, meanwhile restricting eligibility reduced NBs by 64%. CONCLUSION:Adult respiratory vaccinations in Sweden provide substantial value for the healthcare system, economy and society, with estimated benefits exceeding costs under modeled assumptions. These findings may inform policy discussions on strategies to sustain or expand vaccination budgets, improve access and increase uptake, particularly among at-risk populations.
BACKGROUND:Vaccine-preventable illnesses, such as pneumococcal disease, respiratory syncytial virus, influenza, and COVID-19, place a significant burden on Spain's population health, health system, and economy. However, uptake and funding constraints limit the full value potential of Spain's national immunization programs. METHODS:A benefit-cost analysis was performed to assess the societal return on investment from adult vaccination by estimating benefit-cost ratios and net benefits (NBs). All outcomes were monetized using established methods. Program costs included all direct vaccination-related expenditures. Scenario and sensitivity analyses were performed to assess alternative program specifications and to test the robustness of the model. RESULTS:Spain's age-based respiratory immunization programs generate lifetime societal benefits of €1.9 when monetized mortality risk reduction is age-adjusted, and €7.0 per €1 spent when monetized equally across all ages. This corresponds to NBs of €5.4 to €36.4 billion. Introducing adult RSV vaccination could increase NBs by up to 41-21% compared to the status quo. Additionally, improving uptake across all programs would increase NBs by 134-101%. CONCLUSIONS:Spain's adult respiratory vaccination programs generate positive socioeconomic returns. Including adult RSV vaccination and increasing vaccination uptake in general could further increase their societal benefits. Realizing these gains requires adequate public investment to improve vaccine uptake.
INTRODUCTION:Pertussis remains an unsolved public health problem. We have synthesized recent evidence on the immunogenicity, effectiveness, and safety of the two available vaccines, whole-cell (wP) and acellular (aP). We aimed to reorient current thinking and critically address some widely held misconceptions about pertussis vaccines. AREAS COVERED:We conducted a targeted literature review to identify studies published in the last 10 years, describing aspects of effectiveness, safety, and the immune response to wP and aP. EXPERT OPINION:Vaccines containing wP and aP continue to successfully achieve their historical goal of preventing pertussis deaths in children. Contrary to widely held beliefs, wP vaccines do not completely prevent colonization and have not been proven to prevent transmission. Both vaccines demonstrate clinically significant effectiveness against pertussis disease, hospitalization, complications, and death. However, neither provides long-term protection, interrupts pertussis transmission, or prevents cyclic outbreaks. Both require periodic boosters. Differences in the immune response have not been linked to adverse clinical outcomes or reduced efficacy in young children. Both wP and aP demonstrate a favorable benefit-risk profile for preventing severe pertussis in children. However, the reactogenicity and safety profile of aP is clearly superior, which may be a decisive factor for optimal vaccine uptake.
BACKGROUND:Despite the significant impact of longstanding pediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial. Higher valent vaccines, such as the 20‑valent PCV (PCV20), could reduce this burden, yet their value in the contemporary UK setting has not been fully assessed using recent data. RESEARCH DESIGN AND METHODS:An age-structured dynamic transmission model used post-COVID-19 UK epidemiology (2001-2023) to compare pediatric PCV20 (2 + 1 and 1 + 1) with PCV13 (1 + 1) and PCV15 (1 + 1). Over 10 years, we assessed cost-effectiveness and number needed to vaccinate (NNV), capturing disease cases, deaths, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Sensitivity and scenario analyses examined key uncertainties. RESULTS:Over 10 years, both PCV20 schedules were dominant versus PCV13 and PCV15. Versus PCV13, PCV20 1 + 1 and 2 + 1 were projected to avert 448,432 and 499,151 disease cases and save £1.509 and £1.306 billion, respectively. Versus PCV15, PCV20 1 + 1 and 2 + 1 were projected to avert 409,459 and 460,179 disease cases and save £1.424 and £1.221 billion, respectively. NNVs versus PCV13 were lower for PCV20 than PCV15 across both dosing schedules. Sensitivity and scenario results were consistent with the base case. CONCLUSION:Pediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency.
INTRODUCTION Vaccine hesitancy has emerged as a major challenge for pediatric immunization programs, shaped by a complex interplay of structural, relational, and informational factors. In Latin America, these dynamics are further influenced by health system fragmentation and social inequities, requiring approaches that extend beyond information-based interventions.AREAS COVERED This review examines the multidimensional nature of vaccine hesitancy in pediatric populations, with a focus on Latin America. It examines the role of digital environments, clinical communication, and system-level factors, and discusses emerging strategies such as narrative communication and prebunking. The literature was identified through a targeted review of peer-reviewed publications and relevant global health reports.EXPERT OPINION Addressing vaccine hesitancy requires integrated strategies that combine trust-building with anticipatory communication. Approaches such as narrative shielding and prebunking may complement traditional interventions by strengthening how caregivers interpret vaccine-related information. Future efforts should prioritize context-specific implementation and evaluation in real-world settings.
BACKGROUND:Respiratory syncytial virus (RSV) remains a leading cause of medically attended lower respiratory tract disease (MA-LRTD) among infants in Japan. With the approval of maternal immunization (MI) and nirsevimab, Japan is transitioning from high-risk-targeted prophylaxis toward broader RSV prevention. This study evaluated the public health and economic impact of alternative MI and nirsevimab strategies within the Japanese National Immunization Program (NIP). RESEARCH DESIGNS AND METHODS:A static decision-analytic cohort model estimated clinical and economic outcomes from birth through the first year of life (and the second RSV season for eligible high-risk infants). Strategies included an NIP-aligned scenario reflecting expected MI and nirsevimab, mixed nirsevimab-MI coverage scenarios, and nirsevimab-only. Outcomes included MA-LRTDs, hospitalizations, costs, quality-adjusted life-years (QALYs), and number needed to immunize (NNI) from payer and societal perspectives. RESULTS:Compared with the NIP-aligned scenario, shifting coverage toward greater nirsevimab use reduced MA-LRTDs by 9.6% to 28.1%. A nirsevimab-only strategy reduced MA-LRTDs by 34.3% and hospitalizations by 33.4%. Under base-case assumptions, strategies with greater nirsevimab use improved outcomes and reduced costs, with lower NNI as coverage increased. CONCLUSIONS:For the Japanese setting, greater nirsevimab use improves outcomes and reduces costs, with nirsevimab-only strategies providing the greatest overall benefit.
