Vaccine

BackgroundHigh-dose inactivated influenza vaccination (HD-IIV) demonstrates superior effectiveness versus standard-dose vaccination (SD-IIV) in adults aged [≥]60 years. A recent meta-analysis integrated complementary evidence sources of representing over 85 million individuals across 14 influenza seasons. MethodsA previously developed model was updated using life-time horizon and societal perspective. Updated parameters included demographics, costs, hospitalization rates, and relative vaccine effectiveness (rVE): RCT evidence (24% for ILI, 7% for cardiorespiratory hospitalizations) and RCT + real-world evidence (RWE) (15% for ILI, 8% for cardiorespiratory hospitalizations). ResultsHD-IIV resulted in incremental cost-effectiveness ratios of {euro}7,300/QALY (RCT evidence) and {euro}5,800/QALY (RCT+RWE evidence). Implementation would prevent 7,200 general practitioner visits, 6,300 cardiorespiratory hospitalizations, and 269 deaths, by using RCT evidence. Probabilistic sensitivity analysis demonstrated >99% probability of cost-effectiveness at {euro}20,000/QALY threshold for both RCT and RCT+RWE evidence. ConclusionsHD-IIV remains highly cost-effective for Dutch adults aged [≥]60 years under updated evidence scenarios, supporting implementation in the national immunization programme. HighlightsO_LIThe economic analysis of high-dose inactivated influenza vaccine was updated. C_LIO_LIRelative vaccine effectiveness of HD-IIV incorporating recent evidence was used. C_LIO_LIHD-IIV remains cost-effective in Dutch adults aged [≥]60. C_LI

BackgroundOlder adults face a disproportionately high risk of severe influenza, yet the standard inactivated vaccine (IIV) offers suboptimal protection in this population. This study evaluates the cost-effectiveness of replacing IIV with the recombinant influenza vaccine (RIV) for adults aged [≥]50, [≥]65, and [≥]80 years in Hong Kong. MethodsA decision tree model was used to compare RIV with IIV for adults aged [≥]50, [≥]65, and [≥]80 years in Hong Kong, from a societal perspective. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were evaluated with the impact of parameter uncertainty on the results assessed via deterministic and probabilistic sensitivity analyses. ResultsFor adults [≥]50 years, RIV increased total costs by USD5.1 (HKD39.8) per person and gained 0.00012 QALYs (ICER: USD40,659 [HKD317,140] per QALY) compared to IIV. Among adults [≥]65 years, RIV cost USD6.0 (HKD46.8) more and gained 0.00021 QALYs (ICER: USD29,077 [HKD226,801] per QALY). For adults [≥]80 years, RIV cost USD3.2 (HKD25.0) more and gained 0.00015 QALYs (ICER: USD21,092 [HKD164,518] per QALY). ICERs were less than willingness-to-pay thresholds of one to three times Hong Kongs gross domestic product per capita. ConclusionsRIV is cost-effective compared with IIV for adults [≥]50, [≥]65, and [≥]80 years in Hong Kong, with the lowest ICER observed in individuals [≥]80 years.

BackgroundCOVID-19 vaccine hesitancy remains a public health issue despite the fact that vaccines are readily available and recommended for all persons aged [&ge;]5 years in the United States. We aimed to describe parents plan to vaccinate their children in two different populations: families in a prospective, longitudinal cohort study and families experiencing homelessness enrolled in cross-sectional surveillance for acute respiratory infections. MethodsParticipants were parents/guardians of children aged <18 years, recruited either from a serial cross-sectional homeless study in Seattle-King County, Washington or from a household cohort study in the Seattle Metropolitan area. Participants were surveyed during October 2020--May 2021 about their plans to vaccinate their child against COVID-19. Vaccine plans were described by study population as well as by sociodemographic features and over time. ResultsAmong parents of 640 children enrolled in the household study surveyed in October 2021, 66% reported planning to vaccinate their child vaccinated against COVID-19 once vaccines became available. This proportion increased slightly over the study period, to 75% in May 2021. In the homeless study, 1284 surveys were collected from parents of 338 children. The proportion of parents of families experiencing homelessness who planned to have their child vaccinated against COVID-19 ranged from 52% in November 2020 to 16% in March 2021. ConclusionCOVID-19 vaccine plan among parents of children experiencing homelessness in Seattle-King County decreased over time, with the majority of parents reporting that they did not plan or were undecided about COVID-19 vaccination for their children by May 2021. Further investigations are needed among families experiencing homelessness to assess vaccine attitudes and perceived barriers to getting their children vaccinated against COVID-19. SummaryPlans to get vaccinated against COVID-19 was less common in children experiencing homelessness and intent decreased over time during the study, whereas vaccination was acceptable in other families in Seattle, WA

BackgroundTwo RSV immunisations products: a maternal vaccine, Abrysvo, and a long-acting monoclonal antibody, nirsevimab, both designed to prevent RSV illness in infants, have recently become available. Modelling evidence is required to inform how to optimally use these products in immunisation programs to reduce the burden of RSV in young children. MethodsWe extend a dynamic transmission model calibrated to RSV-hospitalisation data of children aged < 5 years in temperate Western Australia (WA) to simulate a range of potential RSV immunisation programs. Using our model, we estimate the impact of both single-product and hybrid RSV immunisation programs. The analysis considers timing of administration, coverage levels and targeting of high-risk groups. Impact on RSV burden is analysed in the context of the WA setting and the possible significant cost differences between the two products. ResultsAll programs analysed were effective in reducing RSV burden. Programs using nirsevimab for newborn infants at similar coverage levels to the Abrysvo programs, averted more RSV-hospitalisations annually. Seasonal programs that focused on protection during high RSV activity and programs targeting high-risk infants were the most efficient in reducing RSV burden. When dose cost is considered alongside program impact on RSV burden, we find evidence to support further economic analysis of hybrid programs as they could mitigate the cost differential between the two products while remaining highly effective in reducing RSV burden. ConclusionsOur study is the first to comprehensively analyse hybrid RSV immunisation programs that use Abrysvo and nirsevimab. RSV immunisation programs can substantially reduce the burden of RSV in young children. Our modelling analysis provides evidence on immunisation type, timing, coverage, high-risk groups and dosage cost that will support decision makers and can be used in economic evaluations.

Background: The value proposition for Shigella vaccines is strengthened by the potential for vaccines to prevent linear growth faltering. However, because expected effect sizes in Phase 3 vaccine trials are small due to limited Shigella incidence, a simple comparison of growth by randomized vaccine arm is likely underpowered and may yield null or even inverse results. Methods: We consider a new approach that estimates vaccine effects in the subgroup that would be infected in absence of vaccination, termed the naturally infected. In simulations parameterized by multi-site studies of diarrhea, we compare power for detecting linear growth effects in the naturally infected versus the full study. We further quantified how power is impacted by trial design choices including immunization schedule, study site, and timing of growth measurements. Findings: Simple comparisons of height-for-age z-score (HAZ) by randomized vaccine arm have extremely limited power (<15%) at realistic trial sizes (n=2,500 to 20,000) and carry risk of showing an inverse effect due to random chance. In contrast, naturally infected effects were five to ten times larger and power was up to three times higher. Using a twelve month immunization schedule with a single growth endpoint in high-incidence settings maximized power to detect an effect. Interpretations: While realistically sized clinical trials may be underpowered to detect an effect of vaccination on growth, estimation using the naturally infected subpopulation and careful trial design improve chances of detecting an effect while mitigating risks of null or inverse results.

BackgroundGiven emerging evidence on the waning of immunity from typhoid conjugate vaccines (TCV), the World Health Organization (WHO) commissioned a multi-model comparison to determine the optimal schedule in terms of health and economic impact to inform updated recommendations for TCV use across different settings. Methods and findingsTo identify optimal vaccination strategies across different incidence settings and vaccine waning assumptions, we compared two agent-based and two compartmental dynamic models of typhoid transmission. All models were fitted to harmonized age-specific incidence data from medium, high, and very high incidence settings. We assessed different TCV schedules under slow- and fast-waning scenarios to evaluate the best age for routine vaccination and the potential need for booster doses and catch-up campaigns. We evaluated the public health and economic impact predicted for each model and scenario using the net-monetary-benefit framework to determine cost-effectiveness under two representative scenarios for the health outcomes and costs of vaccination and treatment. Over a 10-year time horizon, routine vaccination at 9 months with a catch-up campaign to 15 years and a booster dose at 5 years was predicted to have the greatest impact, reducing cases by a median of 48-64% across the incidence settings. Across all four models, TCV introduction with a catch-up campaign was cost-effective at willingness-to-pay (WTP) thresholds >$1,250 per disability-adjusted life-year (DALY) averted in medium incidence settings when costs and case-fatality risk (CFR) are high and in high incidence settings when costs and CFR are low. The optimal strategy was to delay vaccination to 2 or 5 years of age if waning is fast, depending on the age of peak incidence. In very high incidence settings, TCV introduction at 9 months or 2 years of age was cost-saving, and adding a booster dose at 5 years was cost-effective at most WTP values across all scenarios. ConclusionsModel predictions for the impact and cost-effectiveness of different TCV schedules were fairly robust to uncertainty in parameter values and model structure, but the optimal strategy depends on the typhoid incidence rate, CFR, and waning rate of vaccine protection.

BackgroundNeisseria gonorrhoeae poses significant public health challenges due to multidrug-resistant gonorrhoeic and severe reproductive health complications of untreated infection. No vaccine is licensed to prevent gonorrhea. However, the meningococcal outer membrane vesicle (OMV)-containing vaccine, 4CMenB, provides moderate cross-protection against gonorrhea. We have recently demonstrated that immunization with gonococcal OMV accelerates clearance of gonococcal infection in mice compared with 4CMenB. MethodsTo gain insight into possible mechanisms of protection of gonococcal OMV, we evaluated the immunogenicity of GonoVac, a candidate native OMV (nOMV) vaccine against gonorrhea, in mice and rabbits. Three doses of GonoVac were administered intramuscularly from 0.15 to 5 {micro}g in mice, and four doses were used to immunize rabbits at 50 {micro}g per dose, formulated with or without aluminum hydroxide (Al(OH)3). Systemic and mucosal antibody responses were evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay (SBA). Cellular responses were assessed by enzyme-linked immunosorbent spot (ELISpot). ResultsImmunization with GonoVac formulated with and without Al(OH)3 induced significantly higher levels of gonococcal serum and vaginal IgG, and serum bactericidal antibodies, compared with 4CMenB, which induced no serum killing activity. Serum bactericidal activity of GonoVac correlated with anti-gonococcal IgG and IgG2a levels. Serum IgA levels were minimal. Cellular immune responses were higher in mice receiving GonoVac/Al(OH)3 compared with GonoVac alone. Immunogenicity was similar for GonoVac produced in a bioreactor and shake flasks. ConclusionGonoVac elicits robust and functional immune responses in mice and rabbits compared with 4CMenB, supporting its further development as a promising candidate vaccine against gonorrhea. ImportanceGonorrhea, caused by Neisseria gonorrhoeae, remains a significant global health concern, disproportionately affecting populations in low- and middle-income countries (LMICs), particularly women. The emergence of multidrug-resistant strains of N. gonorrhoeae has raised the concern of untreatable gonorrhea, underscoring the urgent need for effective preventive measures. Although there is no licensed vaccine against gonorrhea, the meningococcal OMV-based vaccine, 4CMenB, is partially effective against the disease and has been recommended for use in high-risk groups. In this article, we build on previous findings of enhanced efficacy of gonococcal OMV vaccine candidates compared with 4CMenB in the mouse gonococcal infection model to demonstrate the superior anti-gonococcal immunogenicity of a gonococcal OMV-based candidate vaccine (GonoVac) compared with 4CMenB. GonoVac elicits robust immunity in mice, inducing antibodies that are able to kill gonococci, whereas 4CMenB does not. The findings highlight the potential of GonoVac as a promising vaccine candidate for the prevention of gonorrhea worldwide.

BackgroundInitial reports from the Netherlands indicate a decline in routine childhood vaccination uptake during and after the COVID-19 pandemic, with emerging evidence of reduced parental vaccine confidence. This study aimed to evaluate the long-term impact of the COVID-19 pandemic on routine childhood vaccination uptake. MethodsWe conducted a retrospective nationwide cohort study including all children born in the Netherlands in 2016-2024. First-dose DTaP-IPV vaccination status by age six months was obtained from the national immunisation register. National trends in vaccination uptake across pre-pandemic, pandemic, and post-pandemic periods were assessed using interrupted time series analyses. To further assess the independent effect of the pandemic, a matched-sibling analysis compared vaccination uptake within families before, during and after the pandemic. ResultsInterrupted time series analyses showed significant immediate decreases in vaccination uptake both at the start and end of the pandemic, accompanied by a continuing downward trend during the pandemic (OR 0.984, 95%CI 0.982-0.985) that further declined after its end (OR 0.995, 95%CI 0.994-0.997). In the matched-sibling analysis children eligible during and after the pandemic had lower odds of being vaccinated (pandemic: OR 0.66, 95%CI 0.55-0.80; post-pandemic: OR 0.20, 95%CI 0.17-0.25) compared to their pre-pandemic siblings. Also, later birth order was associated with lower odds compared to first-born siblings (second-born: OR 0.42, 95%CI 0.37-0.48). ConclusionsBoth analyses indicate a negative impact of the COVID-19 pandemic on parental vaccination decisions, which may reflect lingering pandemic effects or new post-pandemic factors, highlighting the need for further research into the drivers of vaccination uptake changes in the post-pandemic era.

Background Ever since the COVID-19 vaccine became available, vaccinations in adolescents lagged behind adults. Whether adolescent vaccination rates were higher in states with "Minor Consent" policies remains unknown. Methods We accessed adolescent (aged 12-17) county-level vaccine administration data from the CDC (12/2020-05/2023). Our outcomes were COVID-19 vaccination counts for: 1) initial dose, 2) completed series doses, and 3) booster doses. Panel Poisson regression models with state and time random effects, seasonal fixed effects, log-population offsets, and adult vaccination rates were estimated to calculate incidence rate ratios (IRR), testing the association between residing in a state with a Minor Consent policy and COVID-19 vaccine uptake. Results Overall, for the initial dose and complete series, there was no difference in adolescent COVID-19 vaccination between states with or without Minor Consent policies. However, we found that Minor Consent policies were associated with lower COVID-19 booster doses (IRR = 0.582; 95% CI: 0.409, 0.828; p = 0.0026). This association was not found in urban counties (IRR = 0.867; CI = 0.722, 1.043; p = 0.1295), but only in rural counties (IRR = 0.541; CI = 0.401, 0.730; p < 0.0001). Conclusions Minor Consent policies were not associated with higher adolescent COVID-19 vaccination. Rather, we found that Minor Consent policies were associated with lower adolescent vaccination for booster doses in rural counties. Despite minimal evidence of impact, states continue to implement Minor Consent vaccination policies. Future research should investigate not just other vaccines, but also how Minor Consent policies impact parental trust in public health more broadly.

Background To anticipate the impact of new pneumococcal vaccines and guide future updates, accurate forecasts of changes in non-vaccine serotypes (NVTs) are needed. We developed and evaluated three models that incorporated different assumptions about the way in which NVTs will increase and generated ensemble predictions for the frequency of NVTs in different post- pneumococcal conjugate vaccines (PCV) periods. Methods We analyzed age- and serotype-specific invasive pneumococcal disease (IPD) cases from the United States CDCs Active Bacterial Core surveillance during the pre-PCV (1998-1999), early post-PCV7 (2000-2004), late post-PCV7/pre-PCV13 (2005-2009), early post-PCV13 (2010-2014), and late post-PCV13 (2015-2019) periods. These data were augmented with IPD cases from several countries and combined with serotype-specific invasiveness to infer serotype-specific carriage prevalence. Three models (Ranking, Proportionate, NFDS-lite) generated independent predictions of post-PCV IPD frequencies, which were integrated using an accuracy-weighted ensemble. Model performance was evaluated using the normalized root mean square error (NRMSE). Results A total of 23,959 non-PCV7 and 15,580 non-PCV13 cases were analyzed. NVT cases increased from the pre-PCV7 to the late post-PCV7 and post-PCV13 periods. The accuracy of predictions across age groups and models was consistent and high during the post-PCV13 periods but varied during the post-PCV7 periods. The Proportionate model (NRMSE=0.70-3.95) outperformed the NFDS-lite (NRMSE=0.93-8.91) and Ranking (NRMSE=1.51-5.37) models during the early-post-PCV7 period, whereas the NFDS-lite model (NRMSE=1.55-9.82) was superior to the Proportionate (NRMSE=1.45-10.22) and Ranking (NRMSE=1.86-11.35) models during the late post-PCV7 period. The Ensemble model improved on these individual models. Conclusions The Ensemble model offers a tool for forecasting serotype patterns to inform pneumococcal vaccines impact and future pneumococcal vaccine formulation.

BackgroundSerotype 3 (S3) has remained a major cause of invasive pneumococcal disease (IPD) despite its inclusion in 13-valent pneumococcal conjugate vaccine (PCV). In October 2023, a 15-valent PCV (PCV15) including S3 was introduced into the Catalan universal childhood immunization program. MethodsWe conducted a retrospective pre-post surveillance study to compare pediatric IPD incidence in Catalonia during a pre-PCV15 period (October 1, 2022-September 30, 2023) and two post-PCV15 periods (October 1, 2023-September 30, 2024, and October 1, 2024-September 30, 2025). All IPD episodes in children <18 years attended in 34 hospitals were included. IPD was defined as detection of S. pneumoniae in a sterile site by culture or PCR. Results323 IPD episodes were identified in 319 children (mean age, 4.5 years). Overall IPD incidence declined from 13.0 to 9.4 episodes per 100,000 children in the first post-PCV15 period compared with the pre-PCV15 period (28% reduction; p=0.02), but returned to baseline in the second post-PCV15 period. S3-IPD incidence decreased significantly from 4.1 to 1.6 episodes per 100,000 (60% reduction; p=0.001) in the first post-PCV15 period and remained lower in the second period: 2.3 episodes per 100,000 (42% reduction compared with baseline; p=0.04). In contrast, IPD incidence caused by PCV7 serotypes increased from 0.3 in the pre-PCV15 and first post-PCV15 period to 2.7 episodes per 100,000 in the second post-PCV15 period (690% increase; p<0.001). ConclusionPCV15 introduction was associated with a sustained reduction in S3-IPD over two years. However, a marked increase in PCV7 serotypes offset overall gains in IPD incidence. SUMMARYPCV15 introduction in Catalonia achieved sustained reduction in serotype 3 invasive pneumococcal disease over two years, but a marked increase in PCV7 serotypes offset the overall disease reduction in the second post-vaccination year.

BackgroundAlthough the impact of COVID-19 vaccination is widely documented in the general population, the evidence on its effectiveness in children under 5 years of age is still limited. In this context, the continuation of vaccination programs in this age group has been debated globally. Consequently, we estimated the effectiveness of the 3-dose series of BNT162b2 (Pfizer-BioNTech) in children aged 6 months to 4 years and the complete 2-dose series of CoronaVac (Sinovac) in children aged 3 to 4 in reducing the risk of hospitalizations due to COVID-19-attributed severe acute respiratory infection (SARI) in Brazil. MethodsWe conducted a retrospective cohort study in 24 Brazilian municipalities, using surveillance data. We evaluated vaccine effectiveness in reducing the incidence rate of COVID-19-attributed SARI hospitalizations from July 2023 to December 2024. Covariate adjustments, defined a priori based on a conceptual model represented by a directed acyclic graph (DAG), were implemented using random-effects Poisson regression models. We also analyzed alternative vaccination schedules and obtained age-specific estimates of effectiveness. ResultsThe cohort comprised 37.6 million person-months of follow-up and 1,384 COVID-19-attributed SARI hospitalizations, including 27 associated deaths. The 3-dose series of BNT162b2 vaccine had an effectiveness of 97% (IRR 0.03, 95%CI 0.01-0.10) in the group aged 6 months to 4 years, with no significant differences among age-specific estimates. No deaths occurred among children who completed the 3-dose series, whereas four deaths were observed among those with fewer doses. The effectiveness of CoronaVac was small and not statistically significant (IRR 0.96, 95%CI 0.57-1.62). However, no deaths were recorded among children who received any number of CoronaVac doses, and no COVID-19-attributed SARI hospitalizations were observed among those who received a third dose of this vaccine. ConclusionsThe 3-dose series of the mRNA vaccine (BNT162b2) had high and consistent effectiveness in protecting against severe COVID-19 in children aged 6 months to 4 years. These findings support the maintenance of routine COVID-19 vaccination in this age group.

BackgroundPost-market vaccine safety surveillance and research are essential to detect and evaluate rare adverse events following immunization (AEFIs) not identified in pre-licensure clinical trials, such as myocarditis post-COVID-19 vaccination. AEFI surveillance infrastructure varies between jurisdictions. Factors that enable or hinder AEFI investigation across diverse settings are not well understood. ObjectiveTo examine clinical, social, and structural/system factors that enable AEFI case identification, reporting, data and biosample collection in high-income countries (HICs) and low-and middle-income countries (LMICs). MethodsWe conducted a qualitative study informed by Interpretive Description in Kenya, South Africa, and Canada. Participants were recruited using purposive and snowball sampling from three groups: (1) key informants with leadership roles in AEFI surveillance and research, (2) healthcare workers, research and laboratory staff involved in AEFI investigation and research, and (3) past participants in vaccine studies. Data were collected through semi-structured interviews and focus group discussions. Thematic analysis was conducted. ResultsEighteen key informants, 47 healthcare workers and research staff, and 27 past research participants were enrolled. Facilitators and barriers were identified across two domains: AEFI surveillance and investigation, and vaccine safety research participation. AEFI surveillance and investigation were shaped by trust in system responsiveness, beliefs and awareness around AEFI reporting, digital innovation, and implementation gaps. Research participation was shaped by altruism and social influence, logistics and research infrastructure, and institutional policies and privacy. Facilitators to AEFI surveillance and research included established policies and procedures for AEFI surveillance, digital tools, emphatic communication, and convenient research processes. Barriers included limitations in workforce capacity, diagnostic testing and funding (especially in LMICs), and cumbersome research approval processes. ConclusionsFindings underscore the need for both globally harmonized standards and locally tailored strategies to support vaccine safety surveillance and research in LMICs and HICs that are patient/participant-centered and include sustainable investments in infrastructure and workforce capacity.

BackgroundCoxsackie B viruses cause acute infections and have been linked to chronic diseases like cardiomyopathies, type 1 diabetes, and celiac disease. Despite their clinical significance, no vaccines exist for coxsackie B virus types. PRV-101, a new candidate vaccine covering five coxsackie B virus types, showed good immunogenicity and tolerability in a phase 1 trial (PROVENT). MethodsWe conducted an extended follow-up of the PROVENT trial to assess the long-term immune response and safety of PRV-101. A total of 26 participants from the original cohort (n=32) were enrolled for additional testing approximately two years post-immunization (11 high-dose, 10 low-dose, and 5 placebo). Coxsackie B virus -specific antibody responses were measured and compared to earlier time points. ResultsPRV-101 was safe with no late adverse effects or emergence of autoantibodies linked to type 1 diabetes or celiac disease. Neutralizing virus antibodies remained elevated, with a clear dose-dependent response. In the high-dose group, antibodies against all coxsackie B virus types reached presumably protective levels, except for coxsackie B virus 2, where two participants turned seronegative. ELISA tests confirmed elevated antibody levels against coxsackie B virus proteins. DiscussionThese results suggest that PRV-101 induces durable antibody responses lasting at least two years. The findings support the continued development of PRV-101 for preventing both acute coxsackie B virus infections and chronic diseases like type 1 diabetes and celiac disease.

Background Post-licensure vaccine effectiveness and impact studies provide evidence on how vaccines perform under routine programme conditions in the real world. In sub-Saharan Africa (SSA), vaccine introductions frequently coincide with concurrent public health and social measures that may influence disease risk and transmission. Failure to account for these concurrent interventions may affect the interpretation of vaccine effects. Methods We conducted a systematic review of post-licensure vaccine effectiveness and impact studies conducted in children under five years of age in SSA. Electronic databases were searched for peer-reviewed studies published between January 2000 and December 2019. Eligible studies used observational designs to estimate vaccine effectiveness or population-level impact. Two reviewers independently screened studies, extracted data, and assessed methodological quality using Joanna Briggs Institute tools. We examined study designs, vaccines evaluated, outcomes assessed, and whether public health and social measures (PHSMs) were measured or adjusted for. A narrative synthesis was undertaken. In addition, we conducted a meta-analysis for rotavirus and pneumococcal conjugate vaccines where we explored the heterogeneity in individual-level effectiveness estimates where designs and outcomes were comparable. Results Sixty-four studies met the inclusion criteria, covering eight vaccine-preventable diseases. Rotavirus vaccines were most frequently evaluated, followed by pneumococcal conjugate vaccines. Case-control and ecological designs were most common, while cohort and time-series analyses were less frequently used. None of the included studies collected, reported, or adjusted for PHSMs such as nutrition, WASH, or access to healthcare. The implications of this omission varied by pathogen. Rotavirus vaccine effectiveness estimates from comparable individual-level designs were consistent across settings, with no evidence of between-study heterogeneity. Pneumococcal vaccine effectiveness estimates showed substantial heterogeneity, which appeared to reflect differences in outcome definitions, host risk profiles, and study context. Estimates for other vaccines were generally protective in direction, although the magnitude and precision varied across studies. Conclusions Post-licensure vaccine effectiveness and impact studies in SSA rarely account for concurrent PHSMs. The consequences of this omission are not uniform across vaccines. For some pathogens, effectiveness estimates appear robust to unmeasured contextual change, while for others they are highly sensitive to outcome choice and setting. Future evaluations should prioritise systematic measurement of key PHSMs and consider study designs that better account for time-varying context. Strengthening routine data systems to capture these factors is essential for generating interpretable evidence to inform immunisation policy.

Pneumonia remains a leading cause of global child mortality. Following the Pneumococcal Conjugate Vaccine (PCV) introduction in Yogyakarta, Indonesia, uptake for the primary series (PCV1 and PCV2) exceeded 90%. However, PCV3 coverage remained suboptimal (60% in 2023; 75% in 2024), indicating significant dropout. This study aimed to identify determinants of PCV immunization completeness and timeliness to address this gap. We conducted a cross-sectional study using cluster sampling among 405 caregivers of children aged 13-37 months in Yogyakarta City in March 2025. Data were collected via structured digital questionnaires assessing socio-demographics, perinatal conditions, knowledge, support systems, and attitudes toward multiple injections. Multivariate logistic regression was employed to determine factors associated with PCV immunization completeness and timeliness. Of 398 participants (98.3% response rate), the majority were female (95.7%) and housewives (75.1%). The prevalence of PCV completeness was 66.3%, while timeliness was only 36.4%. Multivariate analysis revealed that acceptance of multiple injections was the strongest predictor for both completeness (aOR 49.18; 95% CI: 21.30-113.50) and timeliness (aOR 22.04; 95% CI: 6.55-74.08). Additionally, home ownership (aOR 1.93; 95% CI: 1.04-3.58) was associated with completeness, whereas high knowledge (aOR 1.85; 95% CI: 1.12-3.03) improved timeliness. Conversely, preterm birth was significantly associated with lower odds of timeliness (aOR 0.29; 95% CI: 0.09-0.88). Acceptance of multiple injections emerged as the most critical modifiable factor for both outcomes. To optimize the PCV program, health authorities should prioritize counselling strategies to alleviate parental concerns regarding multiple injections. Additionally, intensified monitoring for preterm infants is crucial to mitigate immunization delays.

BackgroundReliable estimates of immunization delivery costs are essential for planning, budgeting, and economic evaluation of vaccination programs. Although a number of empirical costing studies have been conducted in recent years, many low- and middle-income countries (LMICs) continue to lack up-to-date, accurate delivery unit cost estimates--particularly for adolescent and campaign vaccination strategies. Building on prior work, this study aimed to produce updated, standardized country-level estimates of immunization delivery unit costs for different vaccination modalities across all LMICs. MethodsUsing data on study-level unit cost estimates reported by empirical costing studies in the 2024 update of the Immunization Delivery Cost Catalogue, we fitted Bayesian meta-regression models predicting per-dose delivery costs for routine childhood vaccination, routine adolescent vaccination (using human papillomavirus vaccination as a proxy), and vaccination delivered via mass campaigns. Regression models incorporated country-level covariates (per-capita gross domestic product, population size, third-dose diphtheria-tetanus-pertussis vaccination coverage, urbanization, population density, and under-five mortality) and study-level characteristics (cost category, financial versus economic costing perspective, and full versus incremental costing methodology). Fitted models were used to generate country-specific and population-weighted average economic and financial cost per dose estimates for 2024, in 2024 US dollars. ResultsThe analysis included 142 observations for routine childhood vaccination, 63 observations for routine adolescent vaccination, and 113 observations for campaign vaccination. For 2024, the population-weighted mean economic cost per dose across all LMICs was estimated at $5.86 (95% uncertainty interval: $2.74-13.43) for routine childhood vaccination, $17.65 ($7.76-44.30) for routine adolescent vaccination, and $3.13 ($2.03-4.78) for campaign vaccination. Corresponding financial costs per dose were $3.02 ($1.52-6.29), $10.08 ($4.15-25.01), and $1.79 ($1.11-2.91), respectively. Substantial heterogeneity in delivery costs was observed across countries, delivery modalities, and cost perspectives. The estimated associations between predictors and unit costs may be influenced by unobserved study characteristics, and therefore should be interpreted as correlational rather than causal. ConclusionsBy leveraging an expanded empirical evidence base and a Bayesian meta-regression framework, this study provides updated per-dose delivery costs for routine childhood vaccination and estimates new per-dose delivery costs for routine adolescent vaccination and campaign vaccination. As policy decisions often must be made despite incomplete information, these estimates provide a practical source of evidence to support analyses when direct cost data are unavailable.

Objectives: Influenza is a widespread acute respiratory illness posing a major public health challenge for both the National Health Service (NHS) and society, particularly among older adults. This study aimed to assess the cost-effectiveness of high-dose quadrivalent vaccine (HD-QIV) versus adjuvanted quadrivalent vaccine (aQIV) in older adults in Spain. Methods: Public health and economic benefits were evaluated using a decision-tree model considering influenza cases, GP and ED visits, hospitalizations, and influenza-related mortality. Deterministic and probabilistic sensitivity analyses addressed epidemiological and economic uncertainties. Results: From a societal perspective, HD-QIV prevented 54,039 influenza cases, 7,733 GP consultations, 1,585 ED visits, 27,398 episodes of hospitalization due to cardiorespiratory events over a single influenza season and 1,203 deaths compared to aQIV when vaccinating adults [&ge;]65 years old in Spain, resulting in 14,316 LYs and 12,440 QALYs gained over a lifetime horizon. The reduction in health outcomes outweighed the increase in vaccination costs, translating to a reduction in total costs with HD-QIV compared to aQIV. Therefore, vaccinating older adults in Spain with HD-QIV instead of aQIV was a dominant strategy when evaluating hospitalizations due to respiratory and cardiovascular events. HD-QIV remained dominant from a NHS perspective. Sensitivity analyses confirmed the robustness of the model. Conclusions: This analysis showed that vaccinating older adults in Spain with HD-QIV instead of aQIV would reduce influenza cases, GP and ED visits, hospitalizations, deaths, and associated costs, and thus it should be the strategy of choice in a situation of budgetary constraints from either a societal or an NHS perspective.

Influenza A virus can cause severe complications in pregnant women and infants, yet no influenza vaccines are approved for infants younger than six months. To address this, novel maternal vaccination strategies are needed to increase global access and coverage in these vulnerable populations. This study evaluated a hemagglutinin (HA) A/California/2009 (H1N1)-based human adenovirus 5 (huAd5) vector vaccine, adjuvanted with a TLR3 agonist, for its ability to induce influenza-specific passive immunity from pregnant and lactating pigs to their piglets following different immunization routes. Influenza naive pregnant dams were vaccinated via oral, intranasal (IN), or intramuscular (IM) routes three weeks prepartum and boosted four weeks later. Serum, colostrum and milk samples were collected longitudinally to assess HA-specific antibody induced by vaccination. H1N1-Ca/09 neutralizing antibodies were evaluated in serum and IFN{gamma} producing cells were assessed in blood, spleen and lymph node cells. IN and IM routes elicited robust serum HA-specific antibody responses when compared to control animals at one- and four-weeks post-boost, whereas the oral route resulted in poor antibody induction across all samples tested. Piglets nursing from IN and IM vaccinated dams showed a significantly higher level of HA-specific antibodies in serum at 2-3 weeks post-partum compared to control piglets. Notably, IN immunized dams and their piglets showed significantly elevated influenza neutralizing antibodies compared to controls. This work demonstrated that both IN and IM immunization with a huAd5-vectored vaccine robustly induced maternal influenza-specific immunity that supported passive transfer to nursing piglets, with IN immunization resulting in superior transfer of neutralizing antibodies.

West Nile virus (WNV) is the causative agent of fatal West Nile encephalitis. To date, no human vaccine against WNV has been approved. Adjuvants are important for developing effective and affordable vaccines that enhance the immunogenicity and decrease the required antigen doses. In this study, we assessed the efficacy of AddaS03, a synthetic adjuvant analogous to AS03, in a WNV subunit vaccine composed of soluble recombinant envelope protein (sEnv). Using a passive immunization mouse model, we defined the neutralizing antibody titer threshold required for protection against lethal WNV infections and applied this threshold as a surrogate marker to evaluate adjuvant efficacy. AddaS03-adjuvanted formulations elicited markedly higher neutralizing antibody titers compared to Alhydrogel adjuvant 2% (Alhydrogel), even at suboptimal antigen doses, and consistently exceeded the defined protective threshold titer. Moreover, in a sequential challenge mouse model, AddaS03-adjuvanted vaccines completely protected mice from symptomatic WNV infections, whereas Alhydrogel-adjuvanted vaccines failed to confer full protection. Collectively, these findings demonstrate that AddaS03 is a promising adjuvant for WNV subunit vaccine development and highlights the utility of a passive immunization model for defining protective antibody thresholds as a surrogate marker for vaccine evaluation.