Vaccine

Aims: COVID-19 and influenza continue to impose a substantial burden on the Canadian healthcare system, particularly among adults aged greater than 65 years. This study compared the clinical and economic outcomes of a Stand-alone vaccination strategy with separate influenza and COVID-19 vaccines versus a Combination strategy incorporating mRNA-1083, an investigational vaccine targeting both infections. Methods: The study adopted the public healthcare payer perspective and adapted a previously published static model to predict COVID-19 and influenza infections across a one-year time horizon. Relative vaccine effectiveness (rVE) for mRNA-1083 against COVID-19 compared with the stand-alone vaccine (SPIKEVAX) was based on the pivotal clinical trial of mRNA-1083s COVID-19 component (mRNA-1283). For influenza, no incremental VE was assumed versus the adjuvanted stand-alone vaccine (FLUAD). Infections were modeled independently. Clinical outcomes included symptomatic infections, hospitalizations, and deaths. The economically justifiable price (EJP) was calculated at the willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year (QALY) gained. mRNA-1083 uptake was assumed to yield absolute increases in COVID-19 and influenza coverage by 10% and 3%, respectively. Results: Compared with the Stand-alone strategy, the Combination strategy was projected to reduce the number of COVID-19-related symptomatic infections, hospitalizations, and deaths (n=71,074; 5,008; 935, respectively), and corresponding influenza outcomes (n=3,985; 362; 69, respectively). The use of mRNA-1083 within the Combination strategy generated a cost-savings of $90,440,471 in vaccine administration fees and an EJP of $304 per dose. Results were sensitive to rVE, coverage, administration fees, mortality and incidence. Limitations: mRNA-1083s rVE is being evaluated in clinical trials and the impact of mRNA-1083 on vaccine coverage and administration fees is uncertain. Conclusions: mRNA-1083 may reduce the burden of COVID-19 and influenza in adults aged greater than 65 years in Canada, while offering good economic value because it has the potential to increase coverage and VE while reducing administration fees.

Background Despite the significant impact of longstanding paediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial and is primarily driven by nonPCV13 serotypes. Higher valent vaccines such as the 20 valent PCV (PCV20) may provide additional public health and economic benefits, yet their value in the contemporary UK setting has not been fully assessed using recent data. Methods We updated an age structured dynamic transmission model using post COVID 19 UK epidemiology (2001 to 2023) to compare pediatric PCV20 with PCV13 and PCV15. Over a 10 year horizon, we assessed cost effectiveness and number needed to vaccinate (NNV), capturing invasive and non invasive disease cases, deaths, costs, quality adjusted life years, and incremental cost effectiveness ratios. PCV20 was evaluated under 1+1 and 2+1 schedules; PCV13 and PCV15 were assessed under 1+1. Scenario analyses examined key uncertainties. Results PCV20 was estimated to avert more cases and deaths than PCV13 or PCV15, driven by broader serotype coverage and indirect effects. Both PCV20 schedules were dominant or cost saving versus lower valent comparators, with lower NNVs. PCV20s higher vaccination costs were offset by reductions in downstream healthcare expenditures. Conclusion Paediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency, supporting timely adoption.

Suboptimal rotavirus vaccine effectiveness in low- and middle-income countries (LMICs) highlights the need for next-generation vaccines, such as the neonatal RV3-BB vaccine. However, there is uncertainty in the duration of protection and future price of vaccines in development. We aim to identify the conditions under which switching to RV3-BB is optimal in Malawi and Ghana, where the current immunization programs use 2-dose Rotarix and 3-dose Rotavac schedules, respectively. A full incremental cost-effectiveness analysis was performed using a validated transmission model calibrated to country-specific rotavirus data. Over 2025-2034, introducing RV3-BB resulted in the largest rotavirus-related burden reduction compared with the current country-specific programs. At moderate willingness-to-pay (~0.5 time Gross Domestic Product per capita), RV3-BB was preferred over Rotavac if price per dose was <$1.2 in Malawi and <$2.5 in Ghana, and/or if the average duration of protection exceeded 40 weeks in Malawi. The RV3-BB vaccine is likely to be cost-effective in Malawi and Ghana, as well as other LMICs, based on expected pricing and duration of protection.

Background Robust quantitative evidence on the impact of rotavirus vaccines, their potential benefits in countries without vaccination, and strategies to improve performance in low- and middle-income countries (LMICs) is essential for informing policy decisions aimed at sustaining and expanding vaccination programs. Methods and Findings We used an age-structured compartmental model of rotavirus gastroenteritis (RVGE) transmission that accounts for the natural history of infection to estimate vaccine impact across 112 LMICs. The model incorporates country-specific data on demographics, transmission dynamics, vaccination schedules, coverage levels, and vaccine performance. We simulated multiple scenarios, including the continuation of current vaccination programs, vaccine introduction in countries without programs, the addition of a third dose, scale-up of coverage to 95% in low-coverage settings, and suspension of vaccination. We quantified health impacts by estimating cases, deaths, and disability-adjusted life years (DALYs) averted from 2006 to 2024 and projected over 2025 to 2034 using either no vaccination or the current program as counterfactual. We estimated that rotavirus vaccination averted a median of 268 million RVGE cases (95% uncertainty interval [UI]: 228-306 million), 35 million moderate-to-severe cases (95% UI: 30-38 million), 817 thousand deaths (95% UI: 684-928 thousand), and 53 million DALYs (95% UI: 45-61 million) between 2006 and 2024, resulting from 81 countries with vaccination programs out of 112 LMICs. Using the current vaccination as a baseline, we estimated substantial additional benefits for all strategies, except for suspension, which would increase the RVGE burden over the next 10 years. Scaling up coverage to at least 95% across all 112 LMICs, with countries without the vaccine using the 6/10/14-week schedule, could avert a median of 296 million RVGE cases (95% UI: 243-358 million), 832 thousand deaths (95% UI: 694-932 thousand), and 55 million DALYs (95% UI: 45-61 million), respectively. Furthermore, adding a third dose in the 51 countries currently using a two-dose schedule could enhance vaccine impact, averting a median of 123 million RVGE cases (95% UI: 102-145 million), 377 thousand deaths (95% UI: 310-440 thousand), and 24 million DALYs (95% UI: 20-28 million), respectively, compared to the two-dose schedule. Conclusions Our model demonstrates that rotavirus vaccination provides substantial health benefits, with an even greater impact achievable through broader adoption and increased coverage. Adding a third dose to the standard two-dose Rotarix schedule could be an additional strategy to improve vaccine impact in LMICs. These findings support continued efforts to sustain and expand vaccination programs across LMICs. The country-specific, model-estimated rotavirus burden can also inform economic evaluations to guide more effective vaccination strategies.

Introduction. Routine childhood immunisation is frequently disrupted in conflict-affected settings, leaving many children unvaccinated (zero-dose [ZD]). Their vaccination is now a global priority, but published evidence on restoring immunisation services in these settings is limited. We evaluated a nurse-led, community-based Expanded Programme on Immunisation adapted to a conflict-affected setting in Myanmar, focusing on factors associated with full immunisation (FI) among ZD children. Methods. This mixed-methods observational cohort study enrolled children from November 2023 to December 2025; analyses of FI outcomes were restricted to children enrolled >=18 months, with primary analyses focused on ZD children. Associations between programme delivery factors including vaccination opportunity (the ratio of vaccination sessions available to visits required for FI based on age and vaccination schedule [accelerated versus routine]) and FI were assessed using mixed-effects logistic regression with a random intercept for site. Programme cost and qualitative data from document review and questionnaires were also analysed. Results. Of 13,263 children enrolled, 6563 (49%) were in the analytic cohort; 2,684 (20%) were ZD. Among ZD, 452 (17%) were FI at 12 months and 1329 (50%) at 18 months. Accelerated schedule (OR 3.00, 95% CI 1.11-8.13) and greater vaccination opportunity (OR 2.1 per 0.5 unit increase in opportunity, 95% CI 1.8-2.4) were strongly associated with FI at 12 months, with smaller effects at 18 months. The cost per fully immunised ZD child was US$147, primarily reflecting substantial vaccine costs. Qualitative findings indicate that community engagement increased demand and access, but insecurity and logistical challenges limited service continuity and vaccination opportunities. Conclusion. FI improved over time but remained suboptimal through 18 months. Vaccination opportunity and schedule influenced the timing of FI, but sustained follow-up was critical for completion. Community-based delivery enabled restoration of immunisation services where formal systems had collapsed, demonstrating what is possible and what it demands in active conflict.

Background and Objectives: SARS-CoV-2 (COVID-19) continues to mutate, circulate, and adversely impact health and quality of life. While COVID-19 vaccines remain safe and effective, uptake remains low, especially among children, the youngest of whom were not vaccine-eligible until after Omicron and are underrepresented in published research. This study estimated vaccine effectiveness (VE) among under-5-year-olds. Methods: We used Virginia Department of Health surveillance data from June 2022 through October 2022 to conduct a test negative case-control study. We estimated VE derived from odds ratios (ORs) of reported infections using logistic regression among children aged 6-months to 5-years. Results: Using the earliest positive (cases) or negative (controls) post-vaccine-eligible test results, the VE associated with two doses of a COVID-19 vaccine was 78% (95% CI=45%, 93%; p=0.004) in unadjusted analyses and 70% (95% CI=25%, 91%, p=0.023) when adjusting for age, sex, prior testing behavior, and prior reported infections. The adjusted VE was 74% (95% CI=28%, 94%; p=0.025) among those with no prior positives reported and 45% (95% CI=-302%, 97%; p=0.569) among those with a prior positive reported. Conclusions: These results show that even though the vaccine was not closely matched to the dominant variants circulating during the time period analyzed, it was effective at reducing the risk of reported infections. This study adds to the body of knowledge on pediatric COVID-19 VE in an underrepresented age-group and in a rural region, illustrates the utility of surveillance data for evaluation, and can inform vaccine decisions to improve vaccine uptake for young children.

Despite concerns about the spread and pandemic potential of H5N1, there is no commercial H5N1 vaccine. Seasonal influenza vaccines offer some cross-protection against H5N1, but to date there has been no consideration of whether protection differs between the sexes. We investigated immune responses and protection in adult male and female C57BL/6 mice following vaccination with either inactivated H1N1 or H5N1 (LAIV backbone) virus vaccines. Vaccination induced strong homologous antibody responses, with females generating greater total IgG than males against both H1N1 and H5N1 vaccine, which was primarily mediated by greater IgG responses to neuraminidase (NA) than hemagglutinin (HA) protein. IgG cross-recognition of H1N1 also was greater among H5N1 vaccinated females and was primarily caused by greater IgG responses to N1. IgG2b and IgG2c were the primary isotypes generated in response to these vaccines, with females having greater IgG2b responses and greater binding to Fc{gamma}RIV for avian and human NA than males in response to both homologous and heterologous vaccination. Antibody-dependent complement deposition was measured as an FcR-mediated non-neutralizing response against HA and NA and was robust in both sexes. Vaccinated females had greater neutralizing antibody titers than males against the homologous vaccine virus, with limited cross-neutralizing antibodies detected in either sexes. Neuraminidase inhibition titers were greater in vaccinated females than males against the heterologous virus following H1N1 vaccination and against both the vaccine and heterologous viruses following H5N1 vaccination. When H1N1 and H5N1 vaccinated mice were challenged with a lethal dose of A/Texas/37/2024 H5N1, all H5N1 vaccinated mice were protected, regardless of sex. Among H1N1 vaccinated mice, while both sexes were protected against disease, H1N1 vaccinated females cleared virus faster than their male counterparts. These findings highlight that female-biased NA-specific antibodies result in greater cross-protection and should be considered in studies of influenza vaccines. HighlightsO_LIFemales mount stronger IgG responses than males to both H1N1 and H5N1 vaccines C_LIO_LISex differences in vaccine responses are driven by immunity to neuraminidase (NA) C_LIO_LINA inhibition titers are greater in females, supporting broader cross-protection C_LIO_LIH5N1 vaccination confers full protection in both sexes against lethal H5N1 challenge C_LIO_LIH1N1-vaccinated females clear H5N1virus faster than males after lethal challenge C_LI

Background: Mucosal immunity is critical for preventing poliovirus transmission. Despite evidence that infant immunisation protects against poliovirus infection into adulthood, the duration of vaccine-induced intestinal antibody responses remains poorly characterised. Methods: We evaluated poliovirus type-specific neutralising activity and immunoglobulin levels in stool and serum from children in Tanzania who completed routine poliovirus vaccine series (bivalent oral polio vaccine at birth, 6, 10, and 14-weeks, and inactivated polio vaccine at 14-weeks). The study included a longitudinal cohort with four visits over 6 months and a cross-sectional sample of children recruited 1 to 108-months after vaccine series completion. Potential modification by nutritional factors, gastrointestinal infections, and environmental enteropathy was explored. Findings: Among 103 longitudinal and 246 cross-sectional participants enrolled, 33% and 18% had positive poliovirus type-1 (PV1) stool neutralisation, and 66% and 56% had positive poliovirus type-3 (PV3) neutralisation 1 month after vaccination. All were seropositive for PV1 and PV3 across timepoints. Infants followed longitudinally who were stool neutralisation-positive at enrolment had no boost in neutralisation after vaccination, while those stool neutralisation-negative at enrolment experienced a weak boost at 1 month. Stool neutralisation half-life among longitudinal cohort infants was 3.4 months [95% CI 2.6-5.0] for PV1 and 1.7 months [1.4-2.3] for PV3. Moderate evidence suggested concurrent viral intestinal infections were associated with lower neutralisation responses (PV1 p=0.153; PV3 p=0.052). Interpretation: Intestinal antibody responses to poliovirus vaccination were short-lived. The impact of waning intestinal antibodies on transmission risk remains unclear and research is needed to identify vaccination strategies that induce durable mucosal immunity.

Background: Malaria exposure has been hypothesized to alter immune responses to childhood vaccines, but evidence is inconsistent. We evaluated whether early-life malaria exposure and perennial malaria chemoprevention (PMC) modify antibody responses to the 10-valent pneumococcal conjugate vaccine (PCV-10) among infants in a high malaria transmission setting in eastern Uganda. Methods: This study was nested within the MIC-DroP trial (NCT04978272) whereby 202 infants were selected for inclusion. Serotype-specific IgG concentrations were measured using an in-house multiplex seroassay from samples obtained at 8 and 24 weeks of age. Immunogenicity was quantified as the log10 fold-change in IgG concentration between the 8 and 24-week timepoints, and seroconversion as [&ge;]0.35 g/mL at week 24 (i.e., seropositive). Generalized estimating equation models were used to assess associations of PCV-10 immunogenicity and seroconversion with malaria exposure, malaria chemoprevention and birth outcomes. Results: Among the 195 of 202 infants who completed the three-dose PCV-10 series, neither infant PMC nor malaria exposure from study enrollment to 14 weeks were associated with PCV-10 immunogenicity or seroconversion. In contrast, low birthweight (<2500g) was associated with lower immunogenicity (82% lower antibody fold-change, p=0.003) and reduced odds of seroconversion (OR=0.19, p=0.003); preterm birth (<37 weeks) showed similar associations (79% lower antibody fold-change, p=0.018; OR=0.181, p=0.009). Conclusion: In this malaria-endemic setting, early-life malaria exposure and chemoprevention did not measurably alter PCV-10 antibody responses. However, low birthweight and prematurity were associated with reduced vaccine immunogenicity.

Background: The Vaccine Safety Datalink (VSD) detected a statistical signal for ischemic events (ischemic stroke or transient ischemic attack) following bivalent mRNA COVID-19 vaccination through prospective surveillance during 2022-2023. Although multiple studies from other surveillance systems and countries reported no increased risk, important methodological limitations remained. This U.S. study addressed those limitations by evaluating the ischemic stroke risk following bivalent mRNA COVID-19 vaccination, influenza vaccination, and their same-day coadministration using event-dependent self-controlled case series (SCCS) design. Methods: Study outcomes included first-ever ischemic stroke (primary outcome), first-in-1-year ischemic stroke (secondary outcome), and ischemic events (exploratory outcomes), identified using ICD-10-CM codes in inpatient and emergency department settings during September 1, 2022-March 31, 2023, among individuals aged>=12 years across eight VSD sites. Analyses were conducted separately for Pfizer-BioNTech and Moderna bivalent vaccines, with relative incidences (RI) and 95% confidence intervals (CI) estimated for 1-21-day and 1-42-day risk intervals, using person-time outside these intervals as the control period. Subgroup analyses were performed by age group (12-64, >65 years) and history of documented SARS-CoV-2 infection. Results: A total of 6,510 first-ever ischemic strokes were identified among more than 6.8 million participants. Among recipients of Pfizer-BioNTech bivalent COVID-19 and influenza vaccines, no statistically significant increased risk of first-ever ischemic stroke was observed following bivalent COVID-19 vaccination (RI=0.94; 95% CI: 0.63-1.41), influenza vaccination (RI=0.95; 95% CI: 0.82-1.10), or same-day coadministration (RI=1.15; 95% CI: 0.88-1.49) within 1-21-day risk intervals; findings were similar for 1-42-day intervals. Comparable null results were observed for Moderna vaccines and across all subgroups, secondary, and exploratory outcomes. Conclusion: No increased risk of ischemic stroke was found following bivalent mRNA COVID-19 vaccination, influenza vaccination, or their coadministration in this multi-site SCCS study. These findings are consistent with previous studies and underscore the importance of continued vaccine safety monitoring.

Adenoviruses (Ads) are widely used as vaccine vectors. However, pre-existing immunity to commonly used serotypes, like Ad5, can reduce vaccine immunogenicity, with neutralizing antibody titers >200 previously shown to impact vaccine efficacy. Gorilla adenovirus (GRAd) vectors have been developed to evade pre-existing anti-vector responses, but their seroprevalence in southern Africa is poorly defined. Here, we assessed seroprevalence to GRAd32, Ad26 and Ad5 before (baseline) and after COVID-19 vaccination, in cohorts from South Africa and Zimbabwe. Sera from South African participants enrolled in the Sisonke sub-study (n=100, prior to Ad26.COV2.S vaccination) and the follow-up "Booster after Sisonke" (BaSiS) study (n=226) were tested for neutralizing antibodies to Ad5, Ad26, and GRAd32. These samples included paired pre/post boost samples for 27 donors. We also tested sera from the Zimbabwean Mutala cohort (n=131, of which 44 were unvaccinated, and 87 vaccinated with inactivated vaccines). Participants living with HIV (PLWH) comprised 30-50% of each cohort. In the pre-vaccination samples from the Sisonke cohort, geometric mean titers (GMT) for anti-GRAd32, Ad26, and Ad5 antibodies were 78, 142, and 459, with neutralization titers >200 observed in 14%, 32%, and 68% of participants, respectively. Similarly, in the unvaccinated participants in the Mutala cohort, GMTs for GRAd32, Ad26, and Ad5 were 117, 245, and 536, with neutralizing titers >200 in 22%, 42%, and 69% of participants. We observed no significant difference in Ad antibody titers between PLWH and those living without HIV. We next assessed the impact of COVID-19 vaccination on titers. Vaccination with inactivated COVID-19 vaccines (Sinopharm/Sinovac) did not significantly affect Ad5, Ad26 or GRAd32 titers in an unpaired analysis. In contrast, [~]9 months after Ad26.COV2.S vaccination, anti-Ad26 titers for longitudinally sampled participants (n=27) increased 10-fold from a GMT of 141 to 1,426. By comparison, GRAd32 responses were not significantly altered by Ad26.COV2.S vaccination, while anti-Ad5 responses showed a modest <2-fold increase. Our data support previous findings that, whereas anti-Ad5 neutralizing antibody responses are commonly detected globally, GRAd32 responses are less frequent. Importantly, GRAd32 neutralizing responses remained unchanged after Ad26.COV2.S vaccination. HIV status had no significant effect on antibody titers. These results support the use of the GRAd32 vector in upcoming HIV vaccine trials, including in regions where Ad26-based COVID-19 vaccines were widely deployed.

Background Diarrhea remains a leading cause of child morbidity and mortality worldwide. Improved and ongoing estimates of the etiologies of severe diarrhea, particularly in low- and middle-income countries (LMICs), are crucial to inform the use of current vaccines and other interventions and to help prioritize the development of new vaccines. Producing rigorous longitudinal data on the global burden and etiology of pediatric diarrhea requires a geographically broad surveillance network with standardized epidemiologic, laboratory, and analytic protocols. Methods We describe the rationale and methods of the Global Pediatric Diarrhea Surveillance (GPDS) network, a World Health Organization (WHO)-coordinated public health surveillance network investigating the etiology of hospitalized diarrhea among children aged <5 years in LMICs. The GPDS network enrolls children hospitalized with diarrhea at 38 sentinel surveillance sites in 31 LMICs across all 6 WHO Regions. Randomly selected stool specimens were tested by TaqMan Array Card quantitative polymerase chain reaction for 16 enteric pathogens previously associated with pediatric diarrhea. GPDS produces estimates of pathogen-specific attributable fractions and incidence of diarrheal hospitalizations at the global, regional, and country levels. Conclusions As a WHO-coordinated global surveillance network, GPDS evaluates pathogens associated with hospitalized pediatric diarrhea. The network monitors the changing burden of pathogens over time, monitors circulating strains, and generates data to inform decision-making around public health interventions. GPDS also improves global, regional, and country diarrheal disease burden estimates, informs new enteric vaccine development, and potentially provides a platform for future enteric vaccine evaluation.

Background: Statewide immunization data are essential for monitoring vaccination trends and evaluating immunization program impact. In the United States, Immunization Information Systems (IIS) were established in the early 1990s to collect these data; however, operational, legal, and procedural details vary across states and over time. This study summarized differences in IIS characteristics, such as legal requirements and reporting procedures, across U.S. states and jurisdictions over time. Methods: We analyzed survey data from previous work in 2000 and the Centers for Disease Control and Prevention (CDC) in 2012, 2018, and 2024. Our review focused on legislation and reporting requirements for immunization registries across 50 states and 14 jurisdictions, including U.S. territories and Freely Associated States. Results: Between 2000 and 2024, legal frameworks and reporting practices for immunization registries expanded across U.S. states and jurisdictions. The number of states with laws or administrative rules authorizing immunization registries increased from 24 states in 2000 to all 50 states, the District of Columbia, five metropolitan areas, five U.S. territories, and three Freely Associated States in 2024. Over the same period, reporting requirements also became more widespread. The number of states and jurisdictions mandating providers to report immunization records increased from 12 in 2000 to 54 in 2024. Consent policies also changed over time. By 2024, most states and jurisdictions had adopted implicit consent for reporting children's immunization records (41; 64%), while a smaller proportion required explicit parental consent (7; 11%) or implemented mandatory reporting without consent (14; 22%). Discussion: IIS infrastructure and reporting requirements have expanded across U.S. states and jurisdictions over the past two decades, while heterogeneity in consent policies and reporting practices persists. These temporal changes may need to be considered when interpreting IIS data, particularly in longitudinal and cross-jurisdictional analyses.

Tuberculosis (TB) remains a major global health challenge, particularly in low- and middle-income countries such as Mozambique. To address this burden, promising new preventive TB vaccines targeting adolescents and adults are currently in phase III efficacy trials. This study aimed to assess stakeholders perspectives on priority high-risk groups, the challenges in reaching them, and potential strategies for delivering a TB vaccine. We conducted a qualitative study using semi-structured interviews with members of the National TB Program, the National Immunization Program, and the National Immunization Technical Advisory Group. Data were collected between March and July 2024. Our findings suggest that a TB vaccine program in Mozambique should prioritize individuals with comorbidities, especially those living with HIV or diabetes, and close contacts of TB patients, followed by healthcare workers, miners, and incarcerated populations. Although uptake is expected to vary across groups, relatively high coverage was anticipated among people living with HIV, TB contacts, and older adults, as well as healthcare workers, incarcerated individuals, formal miners, and in-school adolescents. To improve uptake, campaign-based strategies using mobile brigades were considered promising approaches to expand coverage. Stakeholder perspectives highlight the importance of prioritizing high-risk groups and adopting context-specific delivery strategies to support the effective introduction of a TB vaccine in Mozambique. Clinical trial numbernot applicable.

Background: The World Health Organization has expanded its recommendations for prophylactic Ebola vaccination for at-risk populations. Durable vaccine-induced immunity is important for sustaining outbreak preparedness in regions with recurrent Ebola virus disease (EVD). We assessed five-year persistence of vaccine-induced immune responses in adults and children from the PREVAC trial. Methods: Two large randomised phase 2 trials (NCT02876328), in adults and children aged [&ge;]1 year, were conducted in four west African countries. Participants were randomly assigned to placebo or to one of three Ebola vaccine strategies: Ad26.ZEBOV followed by MVA-BN-Filo at 56 days; rVSV{Delta}G-ZEBOV-GP followed by placebo; or rVSV{Delta}G-ZEBOV-GP followed by a homologous booster dose at 56 days. After 12 months of follow-up, the primary results were published, participants unblinded to their vaccine assignment, and follow-up continued for 60 months. After Month 24, placebo group recipients were offered active vaccination. Anti Ebola virus glycoprotein Immunoglobulin G (IgG) concentrations were measured for 5 years. Findings: 1401 adults and 1401 children were initially randomized, and 1315 (93.9%) adults and 1322 (94.4%) children attended at least one long-term visit. Retention was high, with 95% followed beyond 1 year and 83% completion at 5-year follow-up. For the three vaccine strategies, antibody geometric mean concentrations (GMC) declined modestly between Months 12 and 24, followed by a stable plateau from Months 24 to 60. At Month 60, antibody GMC were higher in the rVSV-based groups (1099 and 1216 EU/ml for adults; 1982 and 2347 EU/ml for children) than in the Ad26.ZEBOV, MVA-BN-Filo group (252 adults and 645 EU/ml children). Antibody persistence at Month 60 was heterogeneous, varying by age, sex, country, and baseline IgG concentration. Interpretation: Licensed Ebola vaccines induced sustained antibody responses in adults and children for up to 5 years. While the protective antibody level is unknown, these data demonstrate long-lasting immune responses from currently employed vaccine strategies.

Background: Vaccination coverage estimates and case-based surveillance have limitations in evaluating immunization programs. Serosurveillance offers a complementary approach by directly measuring population immunity. We assessed whether serologic analyses across multiple antigens (i.e., measles, diphtheria, tetanus) could provide additional insights into vaccination program performance. Methods: We conducted a matched case-control study among children aged 2- to 10-years-old (n=1286) in Zambia using specimens from the 2016 ZAMPHIA survey. Using previously generated data on measles serostatus, measles seronegative children (i.e., cases) were matched to measles seropositive children (i.e., controls) on sex, age, HIV infection status, and province. Samples were tested for tetanus and diphtheria antitoxin IgG antibodies using commercial enzyme immunoassays. We estimated the odds of tetanus and diphtheria seropositivity by measles serostatus using conditional logistic regression and examined age-specific antibody dynamics. Results: Measles seronegative children had 1.7-fold increased odds (95% credible interval [CrI]: 1.3-2.1) of being tetanus seronegative compared to measles seropositive children. Diphtheria serostatus had no significant association with measles serostatus (odds ratio: 1.3; 95% CrI: 0.9-1.7). Tetanus seroprevalence declined monotonically with age. However, diphtheria seroprevalence initially declined through 5 years of age, then increased again beginning at 6 years of age despite the lack of vaccine booster doses given after the primary series in infancy, potentially from asymptomatic or subclinical infections. Conclusions: Serologic analyses revealed measles serostatus was positively associated with tetanus serostatus (where seropositivity arises only via vaccination and not infection), suggesting children who are measles seronegative are more likely to have missed DTP vaccination. We additionally found that measles serostatus was not associated with diphtheria serostatus, suggesting that antibody responses to diphtheria continue to boost beyond infancy when DTP vaccination is given. Our findings support consideration of DTP booster doses in Zambia to address waning tetanus immunity and further investigation of potential diphtheria carriage and transmission.

Background Pediatric immunizations for Respiratory Syncytial Virus (RSV), including monoclonal antibodies for infants and vaccines for pregnant people, have become broadly available and can prevent severe RSV outcomes in infants. However, quantifying the impact of RSV immunization in prevention of severe pediatric illness at the population-level is limited by lack of RSV case surveillance data. The Massachusetts Department of Public Health (DPH) conducted a modeling analysis using routine public health surveillance data to estimate the state-level impact of new RSV immunization products on Emergency Department (ED) visits and hospitalizations in Massachusetts for highest risk pediatric groups. Methods A scenario projection tool, called R.Scenario.Vax, was utilized to simulate RSV-associated ED hospital encounters by age group in the context of newly available immunizations. ED visit and hospitalization data from the National Syndromic Surveillance Program (NSSP) during the time period 10/08/2017--10/19/2024 were analyzed, scaled to account for changes in RSV testing practices over time and missing encounter volume in historic data, and utilized to inform model fit of a "typical" RSV season. RSV immunization data from the Massachusetts Immunization Information System (MIIS) for the 2023--2024 and 2024--2025 RSV seasons informed high and moderate pediatric RSV immunization coverage scenarios and their impact was compared to a counterfactual reference scenario of no new immunizations. Median projections were quantitatively and qualitatively compared to observed 2024--2025 season data. Percent reduction in hospital encounters and encounters averted per 10,000 population were calculated for each scenario as compared to the reference. Results Projections for the youngest at-risk age groups showed significantly lower RSV-associated ED visits and hospitalizations during the 2024--2025 season for both high and moderate immunization coverage scenarios. Median projections for infants under 6 months old in the highest coverage scenario, wherein nearly all infants were immunized, showed 72.6% lower ED visits and 73.4% lower hospitalizations when compared to the reference scenario, equating to 262 ED visits and 85 hospitalizations averted per 10,000 population. Conclusions Our results support the use of modeling methods for public health insights and suggest that RSV immunizations for infant populations result in significantly lower RSV-related ED encounters in Massachusetts.

Vaccines to prevent infant group B streptococcus (GBS) disease are advancing, with licensure likely based on safety and immunologic endpoints rather than clinical efficacy data. This approach requires robust, generalisable serological thresholds of risk reduction (SToRRs). We combined data from six case-control studies in Europe and Africa to define SToRRs for early-onset (EOD) and late-onset (LOD) GBS disease. Across diverse epidemiological and healthcare settings, anti-capsular polysaccharide IgG concentrations were consistently higher in infants who remained disease free than in those who developed disease. Higher antibody concentrations were required to reduce the risk of EOD than LOD, and higher concentrations were required for serotype Ia than for serotype III. This study provides a quantitative framework to support correlates-based evaluation and potential licensure of maternal GBS vaccines.

Background: Incomplete childhood vaccination undermines individual and herd immunity and increases vulnerability to vaccine-preventable diseases. Understanding local determinants of vaccination adherence is essential for targeted interventions. This study assessed routine immunization completion and dropout patterns among children aged 0-15 months in Bayelsa State, Nigeria. Objectives: To determine vaccination completion rates, identify factors influencing adherence, analyze temporal patterns across immunization milestones, and provide evidence-based recommendations for improving coverage. Methods: A comparative longitudinal study was conducted from March 2023 to July 2024 across three Local Government Areas (LGAs), representing each senatorial district. A total of 369 mother-child pairs (123 per LGA) were enrolled. Data were obtained from health facility immunization registers and supplemented with semi-structured questionnaires. Children were followed through the 6th week, 10th week, 14th week, 9th month, and 15th month immunization visits. Completion rates were analyzed using descriptive statistics and chi-square tests. Ethical approval was obtained from the State Ministry of Health, and informed consent was obtained from all mothers. Results: Completion rates varied across LGAs, with the highest in LGA C (86.2%) and lowest in LGA B (61.0%). Phone-based reminders achieved the highest adherence, outperforming routine and home visit strategies. Progressive attrition was observed along the immunization schedule, with dropout exceeding completion by the 15th month. Principal reasons for non-completion included forgetfulness, travel, and caregiver busyness. Maternal age, education, and occupation significantly influenced adherence, indicating disparities across LGAs. Conclusion: Vaccination adherence is shaped by maternal characteristics and operational strategies. While early-stage coverage is high, attrition increases at later milestones, particularly in LGAs with lower resource engagement. Recommendations: Implement targeted phone-based reminders, milestone-specific outreach, and community engagement programs to reduce dropout, enhance timely completion, and strengthen childhood immunity.

Background: Access to dental care remains a significant challenge for many children in Canada, particularly among low-income and underserved populations. The Interim Canada Dental Benefit (CDB), introduced in October 2022, aimed to reduce financial barriers to oral health care for children under 12 years of age while the Canadian Dental Care Plan (CDCP) was being developed. While emerging evidence has examined program uptake, limited qualitative research has explored parents and caregivers experiences with the Interim CDB. Objective: This study aimed to explore parents and caregivers experiences with the Interim CDB in Manitoba, Canada, including awareness, access, perceived benefits, challenges, and recommendations for program improvement. Methods: A qualitative descriptive study was conducted using semi-structured interviews with 30 parents and caregivers of children under 12 years of age. Participants were recruited primarily through community dental clinics. Interviews were conducted between July 2023 and February 2024, audio-recorded, and transcribed verbatim. Data were analyzed using inductive thematic analysis to identify key themes and subthemes. Results: Seven interconnected themes were identified: (1) limited and uneven awareness of the Interim CDB; (2) inadequate and inequitable communication strategies; (3) barriers to accessing the benefit, including misconceptions about eligibility and complex application processes; (4) dental providers as key facilitators of access; (5) financial relief and improved access to care; (6) gaps in coverage and ongoing financial strain; and (7) participant-driven recommendations for improvement. While the benefit was widely perceived as reducing financial barriers and enabling access to care, challenges related to awareness, communication, and adequacy of coverage limited its overall effectiveness. Participants emphasized the need for improved communication from government, simplified application processes, expanded eligibility, and increased financial support. Conclusion: The Interim CDB represents an important step toward improving access to dental care for children in Canada. However, this study highlights critical implementation gaps related to awareness, accessibility, and coverage. Addressing these challenges will be essential to ensuring the success of the new CDCP and advancing equitable access to oral health care.