Vaccine: X

Background and Objectives: Influenza vaccination has a strong safety record and is effective in reducing pediatric influenza-associated morbidity and mortality. However, pediatric vaccination coverage (VC) has declined since the 2019/20 influenza season in the United States. We estimated the impact of increased vaccine protection (through increased VC and/or vaccine effectiveness [VE]) on pediatric influenza-associated burden during the 2022/23-2024/25 seasons. Methods: We used a compartmental model and laboratory-confirmed influenza-associated hospitalization, VC, and VE data among children 6 months-17 years to estimate influenza burden from 2022/23-2024/25 (the 'baseline' scenario) and the impact of vaccination. We simulated scenarios that (1) increased VC by five percentage points; (2) increased VE by five percentage points; (3) increased VC and VE by five percentage points; and (4) increased VC to levels achieved in 2019/20 (the season with the highest pediatric VC to date). We estimated the difference in hospitalizations and deaths between each scenario and the baseline scenario. Results: Among children 6 months-17 years, an estimated 120,000 influenza-associated hospitalizations and 1,650 deaths occurred across all seasons at baseline. Increasing VC to 2019/20 levels had the greatest estimated impact, reducing hospitalizations by 8,670 (7.2%) and deaths by 130 (7.9%). Increasing both VC and VE by five percentage points reduced hospitalizations by 6.6% and deaths by 6.7%, whereas increasing VC or VE by five percentage points reduced hospitalizations by 3.1% and deaths by 3.2%. Conclusions: Increasing pediatric influenza vaccination coverage back to 2019/20 levels was estimated to significantly reduce pediatric influenza-associated morbidity and mortality.

BackgroundSince the COVID-19 pandemic, parental delays and refusals of well-established, safe, and effective childhood vaccinations have contributed to the resurgence of infectious diseases. This raises concerns that COVID-19 vaccine hesitancy may also extend to novel vaccines for children when introduced in the future. This study examined caregivers, who included healthcare workers (HCWs), perceptions of novel vaccinations for children ages 0-17 years old and intentions to vaccinate children and adolescents ages 12-17 years against COVID-19. MethodsWe conducted a secondary data analysis of a larger cross-sectional survey administered to parents/caregivers of children ages 0-17 years in Lusaka, Zambia, between 13 November and 15 December 2023. Vaccination intention for COVID-19 was specifically focused on caregivers of adolescents ages 12-17 years, following COVID-19 vaccination guidelines during the study. Descriptive statistics were used to explore demographic characteristics, vaccination history, and caregivers COVID-19 vaccination status, along with their childrens routine childhood vaccine histories and perceptions of COVID-19 and novel vaccinations. ResultsAmong 277 caregivers (66.8% women, median age: 35 years), 93.1% reported that their child had received all recommended routine childhood vaccinations. COVID-19 vaccine uptake was higher among HCWs (68.2% with [≥]2 doses) than among community members (40.8%) and having [≥]2 doses was associated with higher COVID-19 vaccine uptake among their adolescents ages 12-17 years. 58.0% of caregivers indicated that their 12-17 years old adolescents had received at least one COVID-19 vaccine dose. Overall intention to further vaccinate children against COVID-19, especially among those already unvaccinated, remained low, with 24.7% of caregivers reporting no intent to vaccinate their children. Protection from hospitalization and death from malaria, TB, HIV, pneumonia, influenza, and diarrheal diseases were the most cited reason (79.1%) for intention to vaccinate children with novel vaccines for these diseases. The most prominent reasons for reluctance towards future vaccines were the fear of potential side effects (45.5%) and insufficient knowledge about vaccination benefits and risks (31.8%). Caregivers most trusted the Ministry of Health (86.6%) and healthcare professionals (66.8%) as sources of vaccine information. ConclusionsWhile routine childhood vaccine uptake remained high, acceptance of COVID-19 and future novel vaccines for children was lower and was influenced by caregivers own vaccination status. Targeted and transparent communication through trusted sources such as the Ministry of Health and healthcare professionals may be critical for addressing safety concerns and strengthening confidence in novel childhood vaccines.

BackgroundNipah virus (NiV) is a zoonotic pathogen in the Henipavirus genus that causes severe, often fatal disease in humans. The World Health Organization and the Coalition for Epidemic Preparedness Innovations (CEPI) have designated NiV as a priority pathogen with pandemic potential. While CEPI is funding research on medical countermeasures, including vaccines and monoclonal antibodies (mAbs), there remains limited understanding of how at-risk countries will use them. This study aims to address this gap through targeted interviews and demand forecasting for 10 countries: Australia, Bangladesh, Cambodia, India, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. Methodology/Principal FindingsInterviews with country and global stakeholders gathered data on regional sentiment, financing, and affordability. Profiles were developed to summarize each countrys perceived outbreak risk and their likely use of countermeasures. Demand was estimated by integrating these perspectives into models of likely country-level responses to three NiV outbreak scenarios: Expected, Amplified, and Extended. In the Expected scenario, countries focused on reactive use with global annual demand ranging from approximately 800 to 5,000 doses for vaccine-only, mAb-only, and combination interventions. Ring strategies were preferred given outbreak size and infrequency. Demand was highest for vaccine-only and combination interventions, with lower demand for mAbs-only due to affordability concerns and less familiarity in Bangladesh and India. In Amplified and Extended scenarios, countries expanded their responses to include preventive campaigns for healthcare workers and rural populations. These campaigns would require approximately 410,000 and 6,300,000 doses, respectively, if introduced in all 10 countries. Conclusions/SignificanceThis study has revealed existing sentiments regarding Nipah disease and interventions and modeled demand across three outbreak scenarios. Given global annual demand based on current epidemiology, Nipah countermeasure markets are unlikely to be commercially viable solely on routine country-financed demand. Instead, market health will require external financing and stockpile mechanisms to maintain demand between sporadic outbreaks. Author SummaryNipah virus (NiV), which causes severe and often fatal disease in humans, is recognized by the Coalition for Epidemic Preparedness Innovations (CEPI) as a priority pathogen with pandemic potential. In response, CEPI has supported the development of vaccines and monoclonal antibodies (mAb). However, limited evidence exists on how at-risk countries will deploy these medical countermeasures. We interviewed key decision-makers across 10 at-risk countries, along with global experts on NiV, to better understand disease prioritization, financing and affordability considerations, and countermeasure preferences. Interview findings informed the development of a demand forecast in response to Nipah outbreaks of varying intensity. At expected outbreak levels, countries focused their response on reactive strategies given outbreak size and infrequency. As outbreaks grew in size, countries considered expanding their response to include preventive campaigns targeting healthcare workers and at-risk, rural populations. This study provides new insights into country-level perspectives on NiV and medical countermeasures and quantifies expected demand across three outbreak scenarios and 10 countries. Our findings can provide a foundation for the strategic development of an international Nipah countermeasure stockpile, designed to address episodic NiV outbreaks and enhance pandemic preparedness.

We report general acceptance (79.0%) of Ebola vaccination in the Democratic Republic of the Congo (DRC) between 2023-2024 (n=5,062). Acceptance varied significantly by province with acceptance ranging from 47.6% in Kongo Central to 92.1% in Tshuapa province and was highest among healthcare workers. While Ebola vaccine acceptance and disease knowledge are relatively strong nationally in the DRC, regional differences do exist and may impact future vaccine rollout.

Background Influenza vaccines have seen many changes over recent years in terms of both policy recommendations and product types. Immune responses and vaccine effectiveness vary by vaccine strain composition and product type. This study aimed to explore this variation on a regional level through examining spatial and temporal autocorrelations of vaccine uptake of different product types within Michigan from 2017 to 2021. Methods Influenza vaccine administration data from the 2017/18 to 2021/22 seasons were obtained from the Michigan Care Improvement Registry. Population size estimates for 2017 and 2019 were obtained from the Michigan Department of Health and Human Services. Age-standardized and age-stratified vaccination rates were computed. Disparate county-level vaccine uptake clusters were constructed using spatial autocorrelation indicators and spatiotemporal clusters were identified using scan statistics. Linear mixed effect models were used to study the impact of social vulnerability and urbanicity level on seasonal influenza vaccination rate. Results Vaccination incidence rates for adjuvanted, recombinant, and nasal sprays vaccines and for any vaccines increased significantly through the study period. County-level spatiotemporal clusters of type-specific uptake rates were identified. Most notably, we identified an emerging cluster with high uptake of adjuvanted vaccine radiating from Ottawa County, located in suburban Grand Rapids, and the disappearance of high uptake cluster for high-dose vaccine uptake in the area. Vaccination rates by any product type were found to vary seasonally and showed weak negative association with more rural regions. The overall vaccination rates appear to be lower among counties with higher social vulnerability in certain urbanicity levels, but social vulnerability and urbanicity were not significantly associated with overall vaccination rate during the study period. Conclusions Vaccine type-specific uptake was spatially and temporally diverse in Michigan between 2017 and 2022. Mid and Northern Michigan had consistently relatively lower vaccination rate compared to other regions in Michigan.

Introduction:Although the COVID-19 pandemic clearly showed the potential consequences of a world without vaccinations, vaccine hesitancy is likely to be more pronounced in the post-COVID-19 era. The introduction of human papillomavirus (HPV) vaccines in this context is likely to raise particular concerns. In Tunisia, decision-makers have prioritized the introduction of HPV vaccine into the immunization schedule. This study assessed individual barriers and facilitators to HPV vaccine acceptability in Tunisia, with the aim of guiding an effective communication strategy for HPV vaccination campaigns in Tunisia and neighboring countries in a post-pandemic context.Methods: Using a qualitative design, we conducted 14 focus groups (FG) with healthcare professionals (HCP) (N=32) and community representatives (CR) (N=89) in five regions of the country. The discussion followed a semi-structured guide designed on the basis of vaccine hesitancy determinants matrix. Transcripts were deductively analyzed according to the 'social processes' and 'thinking and feeling' of the behavioural and social drivers (BeSD) Framework. Inductive approach was used to analyze participants suggestions for promoting HPV vaccination.Results:The FG analysis demonstrated that the historically strong trust in vaccination in Tunisia has weakened after the COVID-19 pandemic. Mistrust of health system and experts, the pandemic management and vaccine mandates measures had negative influence on the vaccine attitudes in a post pandemic Tunisian context. Persistent concerns about COVID-19 vaccines safety were frequently intertwined with widespread distrust of pharmaceutical companies and their profit motives, perceived as imposing inequitable access and lower-quality vaccines on countries in the Global South. These concerns fueled confusion about vaccines side effects. The weakening of immunity was recurring, as well as memory issues, impacts on fertility, and sudden deaths. Regarding information, our research revealed that although digital platforms were perceived as widely used, a significant part of the population interviewed considered public TV channel, as the most reliable source of health information.Conclusions: Emphasizing how the pandemic has shaped individual and collective perceptions and attitudes toward vaccination, our findings underline the importance of leveraging lessons learned from the pandemic to develop a context tailored and coherent communication strategy for successful HPV vaccine implementation.

Background Women living with HIV (WLHIV) have an increased risk of persistent human papillomavirus (HPV) infection and cervical cancer. We evaluated the lifetime health impact and cost-effectiveness of HPV vaccination strategies targeting WLHIV across 13 African countries. Methods We developed an age-structured Markov model of HPV infection and cervical cancer in a closed cohort of 100,000 females, stratified by HIV status, and calibrated it separately for each country to age-specific cervical cancer incidence, cervical cancer mortality, and female HIV prevalence. Six HIV-targeted strategies were compared with routine two-dose vaccination at age 14 years. The strategies either provided a booster dose to previously vaccinated WLHIV or combined a booster for previously vaccinated WLHIV with a three-dose primary catch-up course for previously unvaccinated WLHIV. Interventions were delivered at ages 18 or 24 years under standard- and high-coverage assumptions. Outcomes included cervical cancer cases averted, cervical cancer deaths averted among WLHIV, discounted disability-adjusted life-years (DALYs) averted, additional physical vaccine doses, and incremental costs from the health-system and vaccination-programme perspectives. Results All six strategies generated additional health gains relative to routine vaccination alone. Mean DALYs averted across countries ranged from 8.21 for booster vaccination at age 24 years to 81.36 for high-coverage combined booster and catch-up vaccination at age 24 years. Booster-only strategies produced the greatest health gains per additional physical vaccine dose, whereas the high-coverage combined strategy at age 24 years produced the largest average absolute health gain. However, the relative performance of vaccination at ages 18 and 24 years varied by strategy and country. From the health-system perspective, 68 of 78 country-strategy comparisons were more effective and less costly than routine vaccination after accounting for avoided cervical cancer treatment costs. From the vaccination-programme perspective, all strategies required additional expenditure. Conclusions HPV vaccination strategies targeting WLHIV generated additional health benefits beyond routine adolescent vaccination and were cost-saving in many country-strategy comparisons when avoided cervical cancer treatment costs were included. Booster-only strategies were the most dose-efficient, whereas combined booster and primary catch-up strategies produced larger absolute health gains. The relative performance of strategies delivered at ages 18 and 24 years was context dependent and should not be interpreted as evidence of a universal advantage of later vaccination. Given the limited direct evidence on the clinical effectiveness and duration of protection following HPV booster vaccination among WLHIV, the booster scenarios should be interpreted as exploratory.

Importance: With a recent shift towards summer seasonal predominance of COVID-19 across much of the US, debate continues over optimal COVID-19 vaccination strategies regarding timing (including summer vaccination), eligibility, and dosing frequency. We evaluated the population-level impact of alternative vaccine strategies to inform US and state vaccine policy. Objective: To compare reductions in COVID-19 hospitalizations under different vaccination timing, eligibility, and dosing frequency. Design: Decision analytical model using a stochastic individual-based model of SARS-CoV-2 transmission, calibrated to US COVID-19 hospitalization incidence from May 2024-April 2025. Setting: Simulated US national population, with additional scenarios representing state-level seasonal patterns. Participants: Simulated population of 5 million individuals with US age structure, stratified by risk group (immunocompetent, high risk with comorbid conditions, or immunocompromised). Exposures: Vaccination timing, universal or age- and risk-based eligibility, and dosing frequency, including a hybrid strategy of universal annual vaccination with a second dose for adults [≥]65 years and immunocompromised adults (US vaccine policy during the study period). Main Outcomes and Measures: COVID-19 hospitalization risk per 100,000 persons by age-risk group, measured among vaccinated individuals and in the total population. Results: If summer COVID-19 vaccination timing is feasible, annual universal vaccination in July minimized risk (441 [95% UI: 423-463] COVID-19 hospitalizations per 100,000 persons among adults [≥]65 years) compared to a counterfactual scenario with no additional vaccination given during the study period (578 [553-601]). If timing does not change, hybrid vaccination minimized risk, followed by semiannual risk-based vaccination (460 [440-487] and 477 [454-499] hospitalizations per 100,000 in adults [≥]65 years, respectively). The advantage of summer timing diminished if vaccine coverage decreased by 5-10 absolute percentage points (25-50% relative decrease). The magnitude of benefit from summer-timed vaccination and semiannual doses in the highest-risk groups varied regionally. Conclusions and Relevance: Although annual COVID-19 vaccination has historically been timed for winter transmission, summer vaccination may avert more hospitalizations if coverage is maintained, especially in states with predominantly summer transmission including Western and Southern states. The comparative impact of vaccination strategies, especially the benefit of a semiannual dose in the highest-risk groups, may vary regionally. COVID-19 vaccination timing and eligibility may warrant reconsideration.

Background: Filoviruses, specifically Ebola virus (EBOV), Bundibugyo virus (BDBV), and Marburg virus (MARV), have been the etiologic agents of multiple outbreaks of severe disease in the Democratic Republic of the Congo (DRC). Two EBOV-specific vaccine regimens have been approved for use in outbreak scenarios, including the Ad26.ZEBOV/MVA-BN-Filo (Zabdeno/Mvabea) two-dose vaccine, where the MVA-BN-Filo booster dose contains EBOV, MARV, and Sudan (SUDV) virus glycoproteins (GPs) and the nucleoprotein from Tai Forest virus. While long-term immunogenicity of up to two years has been found in clinical trial settings, limited real-world data exists. Methods: Using a multiplexed immunoassay, samples (n=698 at baseline) collected in Mbandaka, Equateur province, DRC, between September 2023 and October 2024 were assessed for seroreactivity to six filovirus antigens (1 BDBV, 2 EBOV, 2 MARV, and 1 SUDV) at three distinct periods: baseline/pre-vaccination, 6-8 weeks post-first dose (Zabdeno), at booster administration (Mvabea), and one-year post-boost dose. Results: Substantial filovirus seroreactivity was found at baseline, with 48.7% (n=340/698) of individuals being seroreactive to at least one virus antigen. High baseline seroreactivity was found against BDBV GP (31.1%, n=217/698), with lower baseline seroreactivity to EBOV GP (15.5%, n=106/698), comparatively. Overall EBOV GP seroreactivity increased to 66.8% (n=376/563) at one year-post vaccine boost and 57.6% (n=250/434) of participants were seroreactive. Despite the booster dose inclusion of SUDV GP and MARV GP, there were no substantial increases in reactivity against either antigen at subsequent timepoints. Overall filovirus seroreactivity increased at all timepoints for the entire cohort, although filovirus reactivity decreased over the study period for those who were seroreactive at baseline. Findings: These data highlight detection of significantly elevated seoreactivity to EBOV GP following first-dose administration of Ad26.ZEBOV, which remained relatively stable one-year post-booster dose administration. Additionally, this study identifies high levels of baseline seroreactivity to BDBV GP despite no previous documented outbreaks in this region of DRC. These data suggest that vaccination with the Ad26.ZEBOV-MVA-BN-Filo vaccine induces stable seroreactivity against EBOV GP, but not to other filovirus antigens.

ABSTRACT Background: Poliomyelitis remains a major public health concern where population immunity is incomplete and circulating vaccine-derived poliovirus (cVDPV) persists. Although Nigeria interrupted wild poliovirus (WPV) transmission in 2020, cVDPV cases continue to pose challenges, particularly in parts of northern Nigeria. Modern control strategies require a synergy of routine immunization, supplementary campaigns, disease surveillance, and community trust. Methods: This multicentre descriptive cross-sectional study evaluated community knowledge and attitudes towards polio immunization across 37 Local Government Areas (LGAs) in 20 states and the Federal Capital Territory (FCT). A multistage sampling strategy was utilized to select 1,850 adult respondents (50 per LGA) spanning rural, semi-urban, and urban settlements. Results: Overall, 40.4% (n = 747) of respondents demonstrated good knowledge, while 58.4% (n = 1,080) displayed positive attitudes towards polio immunization. A striking disparity was observed across residence classifications: respondents in urban/semi-urban LGAs exhibited significantly higher levels of good knowledge (51.7%, 569/1,100) compared to those in rural LGAs (23.7%, 178/750; {chi} = 144.00, df = 1, p < 0.001). Main sources of information were Questionnaire responses (53.6%) and community and Traditional leaders(17.2%). Conclusion & Recommendations: Substantial knowledge deficits persist in rural northern Nigerian communities despite generally favorable attitudes. Interventions must prioritize localized risk communication, involvement of traditional/religious leaders, strengthening routine primary healthcare integration, and targeting zero-dose children in hard-to-reach areas. Keywords: Poliomyelitis, Oral Polio Vaccine, Vaccine Hesitancy, Northern Nigeria, Community Health, Routine Immunization.

There is currently no clinical data for the effectiveness of the only licensed Ebola virus disease vaccine (Ervebo) against Bundibugyo virus disease. A number of studies have shown immune cross-reactivity with Bundibugyo virus after Ervebo vaccination. However, antibody recognition of Bundibugyo is around 2.8-fold lower than recognition of Ebola virus. Here, we aimed to infer how a 2.8-fold drop in immune recognition may affect Ervebo protection against Bundibugyo virus disease based on analysis of data on Ervebo immunogenicity and protection from Ebola virus disease. This work has three main components. Firstly, we analysed the timing of vaccine protection in the Ervebo pivotal ring vaccination clinical trial. Secondly, we performed a systematic review and meta-analysis of antibody responses to Ebola virus after Ervebo vaccination over time. Thirdly, we combined these data with previously reported data on the cross-reactivity to Bundibugyo virus to infer protection of Ervebo against Bundibugyo virus disease. We find that the clinical trial data for Ervebo supports vaccine protection beginning earlier than 10 days after vaccination. Secondly, binding antibody levels against Ebola virus on day 28 post vaccination (peak responses) were on average 12.9-fold (95% confidence interval, CI: 6.4 - 26.0) higher than on day 7, 6.3-fold (95% CI: 3.7 -10.8) higher than on day 10, and 2.5-fold (95% CI: 1.4 - 4.4) higher than on day 14 (neutralising antibodies showed similar results). Finally, we consider the scenarios where antibody levels to Ebola virus at day 7 or 10 are putative protective thresholds against Ebola virus disease, and we assume these thresholds also apply for Bundibugyo virus disease. Then, with a 2.8-fold reduction of responses to Bundibugyo compared to Ebola virus, we predict antibody responses to Bundibugyo virus after Ervebo vaccination are likely above these putative protective thresholds.

Background: Recombinant (RIV) and cell culture-based inactivated (ccIIV) influenza vaccines could improve seasonal influenza prevention; however, evidence is limited in how protection may differ among non-egg-based vaccines. Methods: We conducted a randomized trial of RIV versus ccIIV to compare vaccine immunogenicity in adults aged 18 to 64 years during the 2024-25 influenza season (ClinicalTrials.gov, NCT06518577). Active surveillance for influenza-like illness was conducted for six months post-vaccination and cumulative incidence of influenza by vaccine type was compared to estimate relative vaccine efficacy. Participants were tested for influenza by reverse-transcription polymerase chain reaction or rapid antigen tests. Immunogenicity was evaluated by hemagglutination inhibition (HAI), virus microneutralization (MN), and neuraminidase inhibition (NAI) assays in a subset of blood specimens collected pre-vaccination and one-month post-vaccination. Results: Among the 591 participants, 25 cases of influenza A were detected; 2.4% cumulative incidence among RIV recipients versus 6.1% among ccIIV recipients. The probability of influenza was 61% lower with RIV than ccIIV (95% confidence interval: 7 to 84). Among 151 participants, post-vaccination HAI and MN titers vaccine components were higher among RIV recipients while NAI titers were higher among ccIIV recipients. Conclusions: RIV provided better protection than ccIIV against influenza A illness in adults during the U.S. 2024-2025 season.

Routine infant vaccination has helped reduce cases and deaths from diphtheria, tetanus, and pertussis globally. However, these diseases continue to pose serious health risks as protective immunity wanes over time. Three booster doses of diphtheria-tetanus-pertussis-containing vaccine (DTPCV) administered from 12-months to 15-years of age increase duration of protection beyond childhood. Growing demands on government health spending underscore the importance of understanding the health and economic impact of vaccines prior to introduction. Using an integrated multi-disease epidemiological-economic model, we estimated the health impact (cases averted, deaths averted, and changes to population immunity) and budget impact of introducing DTPCV booster doses in Uganda. Compared to no DTPCV boosters, introducing all three booster doses is projected to result in 2.2 times the proportion of the population protected against symptomatic diphtheria and 2.8 times against tetanus infection among Ugandans under 15 years of age by 2039. Compared to introduction of the early childhood booster (EC) at 18 months of age, introducing all three DTPCV boosters simultaneously is projected to avert 3.2 times the number of tetanus cases over fifteen years at 2.4 times the incremental cost. The projected government vaccination cost per planned dose was USD 0.58 for simultaneous introduction of all three boosters compared with USD 0.68 for the EC booster alone. The average annual incremental cost of all three DTPCV booster doses is USD 2.79 million. Under modelled assumptions, simultaneous introduction of all three DTPCV booster doses in Uganda provides the greatest health gains, with a lower government vaccination cost per planned dose than introduction of the EC booster alone, but may still pose affordability challenges for Ugandas government.

Prior work has shown that school-age children's influenza activity precedes that of adults by one to two weeks. Whether this is robust across outcomes or constant across a season's course is unexamined. Using electronic health record data from two health systems in South Carolina (2016-2026) on individuals with an influenza diagnosis or positive test, we tested age-group lead-lag relationships across six measures using differenced cross-correlation and Granger causality, with significance confirmed via heteroskedasticity-robust block permutation. We tested whether relationships differed between a season's growth and decline phases. Children 5-17 years led every other age group by approximately one week in four out of six outcomes and were the only group showing any nonzero-lag relationship across 60 pairwise combinations. A screen of 150 source-target combinations identified 26 permutation-confirmed instances of children's lower-acuity activity preceding elevated emergency department or inpatient burden in other age groups. The same-outcome lead was concentrated during a season's growth phase, while the cross-severity lead was robust throughout both a season's growth and decline. School-age children's influenza activity is a robust, multi-outcome leading indicator with distinct transmission-timing and severity-progression signals in different phases of seasonal epidemics, supporting incorporation of age-stratified, phase-aware indicators into influenza forecasting.

Importance: In the US, Human papillomavirus (HPV) related cancers cause significant morbidity and mortality, yet HPV vaccine is underutilized. Vaccination is recommended routinely at age 11-12 years but can be given at 9 years. There is controversy about whether earlier introduction would increase completion of the HPV series before by age 13 years or whether it might decrease rates of delivery of other routinely recommended vaccines at 11-12-years [quadrivalent meningococcal conjugate (MenACWY) vaccine, and tetanus-diptheria-acellular pertussis (Tdap) vaccine]. Objective: To determine whether introduction of the HPV vaccine at ages 9-10 versus 11-12 years, results in earlier median age of series completion (primary outcome) and higher rates of initiation and completion by age 13 years. We also examined the effect of earlier introduction of HPV on rates of Tdap and MenACWY initiation and completion by age 13 years. Design: Two-arm cluster-randomized trial involving 31 pediatric practices in Colorado and California between 10/2021-4/2026. Practices were randomized using covariate constrained randomization within each state to Intervention (introduction of HPV vaccination at ages 9-10) or Control (introduction at ages 11-12). Both study groups received similar annual training about best practices for HPV vaccination with recommended initiation age as the only difference. Results: Age at HPV series completion was substantially earlier in the Intervention group (median 12.2 v. 13.3 years; adjusted hazard ratio [aHR] 2.37; 95% CI 1.94-2.89). Key secondary outcomes were also improved in the intervention group: age at series initiation (median 11.0 v. 11.8 years; aHR 2.19; 95% CI 1.84-2.62), series completion by 13 years (61.6% v. 45.1%; RR 1.37; 95% CI 1.04-1.74), and vaccine initiation by age 13 years (77.1% v. 67.0%; RR 1.15; 95% CI 1.00-1.33). The intervention group was more likely to receive Tdap (aHR 1.47;95%CI 1.13, 1.92) during the trial; receipt of both vaccines by age 13 years did not differ. Conclusions: Earlier introduction of HPV vaccination resulted in earlier age of series completion, and more adolescents initiating and completing the series by age 13 without decreasing rates of other routinely recommended vaccines. Our findings support a preferential recommendation at 9-10 years. Trial registration number: NCT04722822 ClinicalTrial.gov

Introduction Vaccination against human papillomavirus (HPV) is the most effective strategy for preventing cervical cancer. We evaluated HPV Vaccine Integrated Service Implementation (HPV-VISION), a program aimed at integrating HPV vaccination with adolescent health (AH) services and the Expanded Program on Immunization (EPI) to improve vaccine uptake among girls aged 9 to 14 years in rural Ethiopia. Methods This mixed-methods implementation study was implemented in four woredas testing two models of integrating HPV vaccination into routine health services: integration with EPI and with an AH service package. We used program monitoring data; exit interviews, in-depth interviews, and focus group discussions with adolescent girls and caregivers; key informant interviews; and costing data. We analyzed effectiveness using negative binomial generalized estimating equation models with facility-level monthly HPV vaccinations as the primary outcome. We analyzed exit interview data descriptively across models. We analyzed qualitative data thematically and conducted a costing analysis. Results The HPV-VISION program delivered 25,821 HPV vaccinations from March to August 2025. Adjusting for baseline differences, facilities in the AH model delivered, on average, 34% fewer HPV vaccinations per month compared to those in the EPI model (adjusted IRR: 0.66; 95% CI: 0.51-0.87). Nearly all girls said they would be happy to receive services again at the place they were interviewed (EPI: 94%, AH: 98%). Experience of care was positive overall with individual measures varying across models. The incremental delivery cost (excluding vaccine cost) per vaccinated girl was USD $7.54 in the EPI model and USD $14.28 in the AH model. Conclusion We recommend that HPV vaccine delivery incorporates integration with AH services and routine vaccination to most efficiently reach underserved girls. An optimal mix of integration with the EPI program and AH services should be based on regional HPV vaccination indicators, other AH needs, population demographics, and costs of the models.

Background: Nigeria introduced single-dose HPV vaccination for girls aged 9-14 in 2023, reaching approximately 60% aggregate coverage by 2025. While an important achievement, this remains short of the 90% coverage called for under the WHO's 90-70-90 cervical cancer elimination targets, and further scale-up depends on reaching out-of-school girls. In this study we used a model of HPV transmission in Nigeria to quantify the residual cervical cancer burden under continued adolescent delivery, assess how additional screening scale-up and equity assumptions modify it, and identify the effective coverage requirements for an infant HPV vaccination program to be non-inferior to the existing adolescent strategy. Methods: We used HPVsim, an agent-based microsimulation calibrated to Nigerian sexual behavior, HPV prevalence, and cervical cancer incidence, to project new cervical cancer cases and age-standardized incidence over 2025-2100 under scenarios which vary vaccination delivery mode (status-quo adolescent, WHO 90-70-90 adolescent scale-up, and 60/75/90% infant delivery), screening coverage (opportunistic 15% vs. scaled 70% aggregate), and the degree to which primary school completion correlated with vaccination (odds ratio 1 vs. 5) and with screening (odds ratio 1 vs. 3). Infant delivery scenarios were run at hypothetical effective-vaccine-efficacy-at-exposure values of 50%, 70%, and 95% - scenario inputs bracketing the plausible waning range, not evidence-based estimates of infant vaccine performance (no HPV vaccine trial has enrolled anyone below age 10). Each scenario was run at 50 replicates (10 calibration draws, 5 seeds); reported outcomes are the median across replicates and uncertainty ranges are interquartile (25th-75th percentile). Results: Continuation of Nigeria's current adolescent program is projected to avert 1.82 million cervical cancer cases (IQR 1.65-1.90 million; 95% UI 1.39-2.02 million) over 2025-2100 (a 53% reduction relative to no vaccination, IQR 51-55%; 95% UI 46-58%), with age-standardized incidence falling from 19.7 to 7.8 per 100,000 by 2100. However, 82% of the near-term (2025-2075) burden is projected to fall on the pre-2015 birth cohort, i.e. women already beyond the vaccination target age, leaving approximately 945,000 residual cases (IQR 905K-1.00M; 95% UI 835K-1.14M) in this cohort. Scaling up screening to WHO targets was estimated to avert a further ~387K cases (IQR 331-424K; 95% UI 269-515K), roughly 25% of the residual burden; results were about 6-8% better if the scale-up instead reached all women equitably regardless of education. Under a hypothetical scenario of infant vaccination at 90% coverage and 95% effective vaccine efficacy at exposure (matching adolescent-age performance), outcomes were comparable to full WHO adolescent scale-up (49% vs. 54% reduction in vaccine-targetable cohort cancers), but under a hypothetical 50% effective efficacy at Nigeria's DTP3-anchored 62% coverage the strategy averted only a fraction of these cancers. Conclusions: The near-term cervical cancer burden in Nigeria is dominated by cohorts vaccination cannot reach; scaling screening for them is the more consequential lever over the coming three decades and rests on established evidence. Findings on infant HPV delivery are exploratory and hypothesis-generating: they depend on three unverified empirical prerequisites - infant HPV vaccine immunogenicity in the first months of life, durability of protection across the ~15-25-year interval to peak HPV exposure, and coverage achievable through Nigeria's routine childhood immunization platform - and should not be read as a basis for any policy recommendation contingent on infant HPV delivery until those prerequisites are established.

Background/Objectives: Older adults are at high risk of influenza-related severe disease and complications. HD-IIV, currently recommended for adults [&ge;]65 years, is egg-based and may be subject to egg-adapted mutations. An mRNA-based vaccine for influenza, mRNA-1010, has been approved by the Food and Drug Administration. Given the clinical benefits observed in mRNA-1010 clinical trials and potential to avoid egg-adapted mutations, this analysis explores the clinical impact of mRNA-1010 compared to HD-IIV in those [&ge;]65 years in the United States. Methods: This study used a decision-analytic model of influenza infection and downstream outcomes to project influenza burden with each vaccine over a one-year timeframe. Vaccine coverage, HD-IIV vaccine effectiveness (VE) and influenza epidemiology was estimated based upon Centers for Disease Control and Prevention data. The relative VE (rVE) for mRNA-1010 vs. HD-IIV was modelled based on data from the clinical trial and published literature on the impact of egg adaptation. Results: The base-case analysis suggests mRNA-1010 may prevent an additional 232,200 symptomatic influenza infections, 130,000 outpatient cases, 21,100 influenza-related hospitalizations, and 2,200 influenza-related deaths compared to HD-IIV. The number needed to vaccination to prevent one hospitalization was 514 or mRNA-1010 vs no vaccine and 404 for HD-IIV versus no vaccine, for an incremental NNV of 110. Scenario and deterministic sensitivity analyses results indicate that clinical outcomes prevented by mRNA-1010 are most sensitive to influenza incidence and VE. Conclusions: mRNA-1010 may improve protection against influenza in US adults aged [&ge;]65 years, leading to meaningful reductions in the clinical influenza-related disease burden in older adults.

Background: COVID-19 vaccination uptake is influenced by various sociodemographic and psychological factors. Previous studies have suggested that the relationship between personality traits and vaccination is context-dependent. However, this association has not been investigated in Japan, a unique sociocultural context characterized by historically low vaccine confidence but exceptionally high COVID-19 vaccine uptake. We examined the association between the Big Five personality traits and completion of the primary COVID-19 vaccination series, exploring potential gender-personality interactions. Methods: A web-based, cross-sectional survey was conducted among 7,210 Japanese adults (aged 20-85 years) in December 2021. Personality was assessed using the Japanese version of the Ten-Item Personality Inventory. Multivariable Poisson generalized estimating equations were used to calculate adjusted prevalence ratios (PRs) and assess gender-personality interactions. Results: Higher extraversion and lower openness were significantly associated with vaccination completion across genders. A significant gender-agreeableness interaction was observed: agreeableness (PR = 1.016, 95% CI: 1.008-1.024) was positively associated with vaccination completion among men but not women. A similar, though only marginally significant, interaction pattern was observed for neuroticism (PR = 1.011, 95% CI: 1.004-1.019 among men). Conclusions: Personality traits act as modest but meaningful, gender-specific psychological modifiers of vaccination behavior in Japan. Public health campaigns should transition from traditional "one-size-fits-all" messages to personality-tailored and gender-responsive communication strategies to optimize vaccine uptake and bolster psychological resilience in future pandemics.

Abstract Background Estimates of the healthcare costs associated with influenza treatment are essential for cost-effectiveness analyses that inform preventative and treatment strategies such as vaccination and non-pharmaceutical interventions. Existing evidence varies across treatment settings, age groups, and countries and there is little data from low- and middle-income settings. Methods We conducted an umbrella review of systematic reviews and meta-analyses reporting direct admitted and non-admitted hospitalisation costs of seasonal influenza treatment in children, adults, and older people. We supplemented an evidence gap with a systematised review of studies reporting adult non-admitted treatment costs. Costs were extracted and adjusted to 2023 USD. We fitted a Bayesian mixed-effects model to estimate influenza treatment costs using national economic indicators, age group, and treatment setting as a priori predictors. We predicted admitted and non-admitted treatment costs for children, adults, and older people in 195 countries and territories. Results Seven reviews were included in the umbrella review, supplemented by 17 primary studies for adult non-admitted care. Extracted data points most frequently described admitted treatment costs and came from high-income countries. The best-fitting model used healthcare expenditure per capita to predict treatment costs, with country-level random effects. Estimated costs increased with healthcare expenditure per capita, were higher for admitted than non-admitted care, and were highest for adults and lowest for children. Conclusions This study provides novel estimates of influenza-associated healthcare costs across age groups and treatment settings by synthesising the available global evidence. By extrapolating to settings without data, our estimates can inform future economic evaluation studies of influenza interventions worldwide.