Search

Sustainable financing for immunization refers to the sufficient and predictable allocation and use of resources to support the achievement of immunization goals within the framework of overall health financing. The Immunization Agenda 2030 (IA2030) agenda spells out four important focus areas needed for sustainable financing: (1) ensuring sufficient and predictable resources, (2) making optimal use of resources, (3) aligning partnerships, and (4) supporting sustainable transitions from external assistance. This paper summarizes the evidence and proposes interventions under each area. While immunization is one of the best investments and justifies public financing, the COVID-19 pandemic has led to the worst economic recession since the Great Depression and threatens countries' ability to mobilize funding to ensure continuity and access to essential services, including immunization. Strategies for ensuring adequate resources differ by income group but include raising more revenues, reprioritizing the budget towards health, and ensuring that health resources favor Primary Health Care (PHC) and immunization. In low- and lower-middle income countries, support from Gavi, the Vaccine Alliance, which channels the largest amount of external financing, will remain important, but some lower-middle income countries will need to prepare for transition. Countries benefitting from the Global Polio Eradication Initiative (GPEI) are also experiencing a transition from GPEI financing to domestic and other external financing. This paper outlines ways in which countries can improve the use of domestic and external resources to better incentivize high-quality PHC and immunization services and align immunization programs with health sector reforms. While governments must lead, collective action from development partners, the private sector, and civil society is needed to promote health system financing systems that ensure that the world is better prepared for future outbreaks and pandemics, while reinforcing the IA2030 vision and making progress towards universal health coverage and the Sustainable Development Goals. [ABSTRACT FROM AUTHOR]

Rotavirus is the leading cause of severe diarrhea in infants and young children. Live attenuated vaccines can lead to horizontal transmission with the risk of vaccine-derived disease in contacts. Transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains leading to clinical disease was not well evaluated in the pivotal clinical trials, and only a few case reports have been described in the literature. We performed a systematic literature review to investigate secondary transmission of RV5 strains to unvaccinated subjects globally. We searched Embase, Medline for English papers, CNKI, Wan Fang for Chinese papers, and other resources (i.e., conference papers with full text) from January 2005 to June 2021. Eligibility criteria for inclusion were original articles based on non-interventional studies (case-control studies, cohort studies, cross-sectional studies) using RV5 strain transmission as outcomes. Other study or publication types were excluded, such as pre-clinical studies, interventional studies and case reports. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used, and study quality was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and the JBI checklist for cross-sectional studies to assess the risk of bias. The search generated 2,089 articles in total. Seven articles met all inclusion criteria, including six cohort studies and one cross-sectional study. All studies underwent quality assessment and complied with the quality criteria of the NOS or JBI checklist, respectively. Overall, none of the seven studies identified RV5 vaccine-type transmission to an unvaccinated population, in either hospitals or nurseries under a close contact environment. One study reported that 1% of unvaccinated infants had gastrointestinal symptoms, but all symptoms were attributed to other clinical conditions. We found no evidence of horizontal transmission of RV5 strains to unvaccinated infants in a context of a limited amount and the descriptive nature of the identified studies. [ABSTRACT FROM AUTHOR]

• Proposed a Multi Criteria Decision Making based Reverse Vaccinology model for predicting Bacterial Protective Antigens. • The proposed model tested on extracted physicochemical features from bacterial protein sequence. • Applied four strategies of Synthetic Minority Oversampling Technique and Edited Nearest Neighbour to handle the data imbalance problem. • Consider MCDM-based TOPSIS and CRITIC methods for order preference with soft and hard ranking model. Reverse vaccinology (RV) is a significant step in sensible vaccine design. In recent years, many machine learning (ML) methods have been used to improve RV prediction accuracy. However, there are still issues with prediction accuracy and programme accessibility in ML-based RV. This paper presents a supervised ML-based method to classify bacterial protective antigens (BPAgs) and identify the model(s) that consistently perform well for the training dataset. Six ML classifiers are used for testing with physiochemical features extracted from a comprehensive training dataset. Selecting the best performing model from different performance metrics (accuracy, precision, recall, F1-score, and AUC-ROC) has not been easy, because all the metrics has the same importance to predict BPAgs. To fix this issue, we propose a soft and hard ranking model based on multi-criteria decision-making (MCDM) approach for selecting the best performing ML method that classifies BPAgs. First, our proposed model uses homologous proteins (positive and negative samples) from Protegen and Uniprot databases. Second, we applied four strategies of Synthetic Minority Oversampling Technique and Edited Nearest Neighbour (SMOTE-ENN) to handle the data imbalance problem and train the model using ML methods. Third, we consider MCDM-based technique for order preference by similarity to the ideal solution (TOPSIS) method integrated with soft and hard ranking model. The entropy is used to obtain weighted evaluation criteria for ranking the models. Our experimental evaluations show that the proposed method with best performing models (Random Forest and Extreme Gradient Boosting) outperforms compared to existing open-source RV methods using benchmark datasets. [ABSTRACT FROM AUTHOR]

A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent vaccine effectiveness (VE) exists across studies and a complete picture is lacking. We searched papers evaluating absolute or relative effectiveness of SARS-CoV-2 BA.1 type or BA.4/5 type bivalent mRNA vaccines on eight publication databases published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events (hospitalization and/or death) was estimated in reference to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses. From 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated higher effectiveness against symptomatic or any infection for all ages combined, with an absolute VE of 53.5 % (95 % CI: –22.2–82.3 %) when compared to unvaccinated and relative VE of 30.8 % (95 % CI: 22.5–38.2 %) and 28.4 % (95 % CI: 10.2–42.9 %) when compared to ≥ 2 and ≥ 3 original monovalent doses, respectively. The corresponding VE estimates for adults ≥ 60 years old were 22.5 % (95 % CI: 16.8–39.8 %), 31.4 % (95 % CI: 27.7–35.0 %), and 30.6 % (95 % CI: −13.2–57.5 %). Pooled bivalent VE estimates against severe events were higher, 72.9 % (95 % CI: 60.5–82.4 %), 57.6 % (95 % CI: 42.4–68.8 %), and 62.1 % (95 % CI: 54.6–68.3 %) for all ages, and 72.0 % (95 % CI: 51.4–83.9 %), 63.4 % (95 % CI: 41.0–77.3 %), and 60.7 % (95 % CI: 52.4–67.6 %) for adults ≥ 60 years old, compared to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses, respectively. The bivalent boosters demonstrated superior protection against severe outcomes than the original monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation. [ABSTRACT FROM AUTHOR]

The vaccine coverage against human papillomavirus (HPV) vaccination remains low in France. The objective of this study was to study adolescent perceptions by comparing boys and girls, in order to build effective school-based interventions. This paper presents a cross-sectional study in French middle school pupils. They completed online questionnaires on their knowledge and attitudes toward the HPV vaccine, HPV vaccination status, their intention, reasons to vaccinate or not to vaccinate, and psychological antecedents of vaccination. A structural equation modeling (SEM) analysis was used to test the hypothesized model. The participants are 818 pupils aged from 12 to 16 years (M age = 13.78). Most pupils were in the pre-contemplative stage (62.7 % of boys and 40.8 % of girls). SEM analysis indicated that the relationship between the level of HPV knowledge, the representations of vaccines in general, and vaccine intention was mediated by attitudes towards the HPV vaccine among both boys and girls. These findings reveal a high percentage of boys who do not feel concerned by the HPV vaccine and highlight the need to consider the psychological antecedents of vaccination in general in addition to the specific attitudes to the HPV vaccine. [ABSTRACT FROM AUTHOR]

• Country ownership is one of the four guiding principles for the Immunization Agenda 2030. • There is little practical guidance on what country ownership is and how to operationalize it. • Measles and rubella programs are used to illustrate country ownership in operation. • Five elements of country ownership - commitment, coordination, capacity, community participation, and accountability - are described. • Our work is a useful guide for immunization program strategy development. Country-owned, as opposed to donor-driven, is a principle within the development sector that recognizes the centrality of countries' leadership, systems, and resources in executing programs and achieving sustainable development. In alignment with this notion, the Immunization Agenda 2030 was developed with country ownership as one of four core principles of the ambitious ten-year plan. This means that the success of immunization programs, including those with eradication and elimination goals such as polio, measles, and rubella, and those with broader equity goals to "leave no one behind" on immunization, would be largely driven by country systems. In this paper we deconstruct country ownership into five operational principles: commitment, coordination, capacity, community participation, and accountability. Through this lens, we illustrate how two countries, Nepal and Nigeria, have exemplified country ownership in their measles and rubella elimination programs and we infer the ways in which country ownership drives system performance and sustains program efforts. [ABSTRACT FROM AUTHOR]

There has been increasing recognition of vaccine access challenges in middle-income countries and the need for increased action, particularly in countries that are not eligible for or have transitioned out of Gavi, the Vaccine Alliance support. These countries' immunization systems are more vulnerable than ever as the COVID-19 pandemic exacerbates existing programme challenges, increasing the risk of delayed vaccine introductions, backsliding immunization coverage rates, and increased coverage inequity. The potential health and equity impact of improving immunization outcomes in middle-income countries is substantial. Modelling suggests that the introduction of pneumococcal conjugate vaccine and vaccines for rotavirus and human papillomavirus in this set of Gavi-transitioned and non-Gavieligible middle-income countries in 2020 could have saved an estimated 70,000 lives if 90 % coverage had been reached. Further, increasing coverage for already-introduced vaccines to 90 % could have saved an additional estimated 16,000 lives. Over the past decade, stakeholders have made considerable efforts to identify immunization challenges in middle-income countries as documented in the 2015 SAGE-endorsed Shared Partner Middle-Income Country Strategy. In the coming decade, new global platforms like Gavi 5.0 and the Immunization Agenda 2030 provide opportunities to align on MIC strategies and provide coordinated global support to middle-income countries. The international COVID-19 pandemic response has the potential to lay the foundation for long term support beyond the scope of COVID-19 to non-Gavi eligible middle-income countries. Meanwhile regional mechanisms to address immunization barriers in middle-income countries have grown in number and strength, offering sustainable platforms for cross-country collaboration and the provision of tailored technical support. To ensure that these opportunities are successfully acted upon and that middle-income countries achieve the Immunization Agenda 2030 goals, comprehensive, multi-stakeholder consultations were conducted to identify areas of action with the greatest potential to accelerate immunization progress. Stakeholders should work together to put these findings, highlighted in this paper, into action, adapting their approaches to specific country contexts and learning from and building on existing efforts. [ABSTRACT FROM AUTHOR]

• Lack of expertise, integrating policy recommendations, and visibility were challenges. • Collaboration, linkages to policymakers, and effective communication were opportunities. • Optimizing the Regional NITAG Network is one of the most promising ways forward. Following the COVID-19 pandemic, the Americas faced a significant decline in vaccination coverage as well as increased vaccine hesitancy. The objective of this paper is to summarize the challenges and opportunities outlined by the National Immunization Technical Advisory Groups (NITAGs) in Latin America and the Caribbean (LAC) and prioritize targeted interventions. The exploratory survey included open-ended questions on two primary components: challenges, and opportunities. Free-text comments presented by each NITAG were collated and classified using indicators and sub-indicators of the NITAG Maturity Assessment Tool (NMAT). Opportunities were classified thematically, and priority actions were generated from the responses. All 21 NITAGs in LAC, representing 40 countries, 76 % of which have been active for over a decade, responded to the survey. The most common challenges were establishment and composition (62 %), integration into policymaking (62 %), resources and secretariat (52 %), and stakeholder recognition (48 %). The distribution of responses was seen across the whole sample and did not suggest a more pronounced need in relation to year of establishment. Opportunities included maximizing the Regional NITAG Network of the Americas (RNA) to facilitate collaboration, information sharing, visibility, and communication; existing global, regional, and systemic analyses; the World Health Organization/Pan American Health Organization (WHO/PAHO) templates for standard operating procedures; twinning programs with mature NITAGs; and NITAGs in governance structures. Action plans were outlined to formalize the establishment of NITAGs and broaden their composition; strengthen decision-making and access to data resources; and enhance the credibility of evidence-based recommendations and their uptake by policymakers and the public. NITAG challenges are not unique to LAC. NITAGs have outlined a short-term prioritized action plan which is critical to enhancing NITAG value and importance in countries. [ABSTRACT FROM AUTHOR]

• Parents' migration status is associated with infant's timely vaccination. • Having a foreign-born mother is positively associated with infant's timely vaccination. • Having a foreign-born father is positively associated with infant's timely vaccination. • Among migrant population, odds of timely vaccination decreases as length of stay increases. • Future research may explore factors behind lower rates of timely vaccination among settled migrants. Migration has been recognized as an important determinant of child health outcomes including childhood vaccination status. This paper aims to examine the association between parental migration status and a less studied aspect of child immunization outcomes, namely timeliness, within the context of New Zealand (NZ), a country characterized by a substantial proportion of its resident population born overseas. Additionally, the study explored the impact of residential duration on children's immunization timeliness. The data was taken from a large, representative population-based cohort study in NZ (Growing Up in NZ study). A total of 6156 children and their parents, comprising 2241 foreign-born and 3915 NZ-born mothers and a sub-group of their partners were included in the analysis. The survey data was linked with the National Immunization Register dataset. Timely immunization was defined as receiving two vaccines at each scheduled vaccination point (at six-week, three-month, and five-month, totaling six doses of vaccines) within 30 days of their due date. We examined the associations between parental migration status, maternal residential duration, and child immunization timeliness while controlling for socio-economic variations. The results were presented as adjusted odds ratios (AORs) with 95 % confidence intervals (CIs). The findings revealed that after adjustment for socioeconomic differences, children of foreign-born mothers exhibited higher odds of receiving all six studied vaccine doses on time compared to children of native-born mothers (AOR 1.51, 95 %CI:1.27–1.78). Similarly, having a foreign-born father was also significantly associated with timely completion of all six vaccine doses. Children of recent immigrants who had resided in the country for less than five years demonstrated higher odds of timely vaccination of all six vaccine doses compared to children of settled immigrants who had lived in the country for five or more years (AOR 1.65, 95 %CI: 1.25–2.19). This study revealed a significant pattern in NZ where immigrants exhibited higher rates of timely immunization for their children compared to native-born parents. However, the findings also underscore the importance of providing support to settled immigrants, as their children experienced declines in timely vaccination rates compared to children of recent immigrants and even those born to NZ-born parents. [ABSTRACT FROM AUTHOR]

The development of an effective combined vaccine represents a crucial strategy for preventing outbreaks of infectious diseases and reducing the burden on healthcare resources. Developing a combined vaccine against both influenza and the coronavirus is a promising approach, but it is still in the early stages of development. This paper reports on a novel combined pentavalent candidate vaccine that has shown promising results in mice, with statistically significant differences in mean antibody titer against the coronavirus and the influenza antigens compared to placebo. We have shown that the coronavirus antigen is capable of inducing an immune response autonomously, regardless of the presence of the influenza antigens in a combined vaccine. On the other hand, the presence of the coronavirus antigen in a combined vaccine showed to enhance the immune response against some of the studied influenza antigens, suggesting that these antigens may act in synergy and elicit an enhanced immune response. The absence of dose-dependent difference in mean antibody titer within the same antigenic groups of vaccine preparations suggested that even small amounts of the coronavirus and the influenza antigens could induce an immune response just as good as high-dose vaccine preparations, which certainly has important safety and cost implications. The vaccine is soon to be ready for clinical trials and mass production. [ABSTRACT FROM AUTHOR]

The U.S. Centers for Disease Control and Prevention (CDC) developed and implemented the CDC COVID-19 Vaccine Pregnancy Registry (C19VPR) to monitor vaccine safety. Potential participants who received a COVID-19 vaccine in pregnancy or up to 30 days prior to their pregnancy-associated last menstrual period were eligible to participate in the registry, which monitored health outcomes of participants and their infants through phone interviews and review of available medical records. Data for select outcomes, including birth defects, were reviewed by clinicians. In certain cases, medical records were used to confirm and add detail to participant-reported health conditions. This paper serves as a description of CDC C19VPR protocol. We describe the development and implementation for each data collection aspect of the registry (i.e., participant phone interviews, clinical review, and medical record abstraction), data management, and strengths and limitations. We also describe the demographics and vaccinations received among eligible and enrolled participants. There were 123,609 potential participants 18–54 years of age identified from January 2021 through mid-June 2021; 23,339 were eligible and enrolled into the registry. Among these, 85.3 % consented to medical record review for themselves and/or their infants. Participants were majority non-Hispanic White (79.1 %), residents of urban areas (93.3 %), and 48.3 % were between 30 and 34 years of age. Most participants completed the primary series of vaccination by the end of pregnancy (89.7 %). Many participants were healthcare personnel (44.8 %), possibly due to the phased roll-out of the vaccination program. The registry continues to provide important information about the safety of COVID-19 vaccination among pregnant people, a population with higher risk of poor outcomes from COVID-19 who were not included in pre-authorization clinical trials. Lessons learned from the registry may guide development and implementation of future vaccine safety monitoring efforts for pregnant people and their infants. [ABSTRACT FROM AUTHOR]

The Sisonke 2 study provided a homologous boost at least 6 months after administration of the priming dose of Ad26.COV2.S for healthcare workers enrolled on the Sisonke phase 3b implementation study. Safety monitoring was via five reporting sources: (i.) self-report through a web-link; (ii.) paper-based case report forms; (iii.) a toll-free telephonic reporting line; (iv.) healthcare professionals-initiated reports; and (v.) active linkage with National Disease Databases. A total of 2350 adverse events were reported by 2117 of the 240 888 (0.88%) participants enrolled; 1625 of the 2350 reported events are reactogenicity events and 28 adverse events met seriousness criteria. No cases of thrombosis with thrombocytopaenia syndrome were reported; all adverse events including thromboembolic disorders occurred at a rate below the expected population rates apart from one case of Guillain Barre Syndrome and one case of portal vein thrombosis. The Sisonke 2 study demonstrates that two doses of Ad26.COV2.S is safe and well tolerated; and provides a feasible model for national pharmacovigilance strategies for low- and middle-income settings. [ABSTRACT FROM AUTHOR]

• Background rates of maternal foetal and neonatal adverse events in South Africa have been assessed to support safety assessment of vaccines. • Retrospective review of paper-based medical records is challenging and time-consuming. • Missing data hampered alignment between clinically-reported adverse events and adverse events confirmed with GAIA case definitions. • Brighton Collaboration GAIA case definitions are useful, but some require amendments to improve utilization in real world settings. Background epidemiologic population data from low- and middle-income countries (LMIC), on maternal, foetal and neonatal adverse outcomes are limited. We aimed to estimate the incidence of maternal, foetal and neonatal adverse outcomes at South African maternal vaccine trial sites as reported directly in the clinical notes as well as using the 'Global Alignment of Immunization Safety Assessment in Pregnancy' case definitions (GAIA-CDs). GAIA-CDs were utilized as a tool to standardise data collection and outcome assessment, and the applicability and utility of the GAIA-CDs was evaluated in a LMIC observational study. We conducted a retrospective record review of maternity and neonatal case records for births that occurred in Soweto, Inner City- Johannesburg and Metro-East Cape Town, South Africa, between 1st July 2017 and 30th June 2018. Study staff abstracted data from randomly selected medical charts onto standardized study-specific forms. Incidence (per 100,000 population) was calculated for adverse maternal, foetal and neonatal outcomes, which were identified as priority outcomes in vaccine safety studies by the Brighton Collaboration and World Health Organization. Outcomes reported directly in the clinical notes and outcomes which fulfilled GAIA-CDs were compared. Incidence of outcomes was calculated by combining cases which were either reported in clinical notes by attending physicians and/ or fulfilled GAIA-CDs. Of 9371 pregnant women enrolled, 27·6% were HIV-infected, 19·9% attended antenatal clinic in the 1st trimester of pregnancy and 55·3% had ≥1 ultrasound examination. Fourteen percent of women had hypertensive disease of pregnancy, 1·3% had gestational diabetes mellitus and 16% experienced preterm labour. There were 150 stillbirths (1·6%), 26·8% of infants were preterm and five percent had microcephaly. Data available in clinical notes for some adverse outcomes, including maternal- & neonatal death, severe pre-eclampsia/ eclampsia, were able to fulfil GAIA-CDs criteria for all of the clinically-reported cases, however, missing data required to fulfil other GAIA-CD criteria (including stillbirth, gestational diabetes mellitus and gestational hypertension) led to poor correlation between clinically-reported adverse outcomes and outcomes fulfilling GAIA-CDs. Challenges were also encountered in accurately ascertaining gestational age. This study contributes to the expanding body of data on background rates of adverse maternal and foetal/ neonatal outcomes in LMICs. Utilization of GAIA-CDs assists with alignment of data, however, some GAIA-CDs require amendment to improve the applicability in LMICs. This study was funded by Pfizer (Inc). [ABSTRACT FROM AUTHOR]

During the height of the global COVID-19 pandemic, the test-negative design (TND) was extensively used in many countries to evaluate COVID-19 vaccine effectiveness (VE). Typically, the TND involves the recruitment of care-seeking individuals who meet a common clinical case definition. All participants are then tested for an infection of interest. To review and describe the variation in TND methodology, and disclosure of potential biases, as applied to the evaluation of COVID-19 VE during the early vaccination phase of the pandemic. We conducted a systematic review by searching four biomedical databases using defined keywords to identify peer-reviewed articles published between January 1, 2020, and January 25, 2022. We included only original articles that employed a TND to estimate VE of COVID-19 vaccines in which cases and controls were evaluated based on SARS-CoV-2 laboratory test results. We identified 96 studies, 35 of which met the defined criteria. Most studies were from North America (16 studies) and targeted the general population (28 studies). Outcome case definitions were based primarily on COVID-19-like symptoms; however, several papers did not consider or specify symptoms. Cases and controls had the same inclusion criteria in only half of the studies. Most studies relied upon administrative or hospital databases assembled for a different (non-evaluation) clinical purpose. Potential unmeasured confounding (20 studies), misclassification of current SARS-CoV-2 infection (16 studies) and selection bias (10 studies) were disclosed as limitations by some studies. We observed potentially meaningful deviations from the validated design in the application of the TND during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

According to recent regulatory guidance, clinical trial objectives should be translated into estimands, i.e., precise descriptions of that what is to be estimated. Hence, estimands are to be formulated for influenza vaccine immunogenicity (IVI) trials, notably for one of the most popular immunogenicity trials, the non-inferiority trial. In this paper an estimand for this trial design is proposed. An estimand should state how intercurrent events are handled. Intercurrent events are events that occur after the start of the trial and that affect the endpoint's measurement or interpretation or prevent its observation. In IVI trials the intercurrent events of interest are immunological intercurrent events (IIEs). Major IIEs are identified, i.e., protocol deviations occurring during the trial that affect immunogenicity endpoints, and the consequences for the trial data collection are discussed. In the statistical analysis endpoint values that are missing or excluded from the analysis due to IIEs are to be substituted by plausible values, by means of multiple imputing. Replacing values are based on predictors of the endpoint. A distinction is made between mandatory and non-mandatory predictors. Mandatory predictors are predictors necessary to prevent biased prediction. Non-mandatory predictors are predictors that limit the additional variance due to the imputing. The four steps of the multiple imputing are explained, and available software is listed. [ABSTRACT FROM AUTHOR]

• We compared the perceptions of patients regarding vaccination and the evaluation of these perceptions by their general practitioners. • Three axes were explored: vaccine safety; vaccine efficacy; 'being in favour of vaccination'. • We observed a correlation between the patient perceptions and their evaluation by the physicians. • The median difference (in absolute values) between physician evaluations and patient perceptions was between 9 and 11 (0–100 scale) for the three axes. • Physicians identified most of the patients with good perceptions regarding vaccination but only a fraction of those with poor perceptions. • This result suggests that doctors need to bear in mind that what they perceive to be their patients' attitudes to vaccination may be wrong, although this should not prevent them from making the case for vaccines. The high level of vaccine hesitancy reported in the French population may lead general practitioners to anticipate difficult discussions on this topic. We aimed to assess the extent to which general practitioners' evaluation of their patients' vaccine hesitancy was correlated with the real vaccine hesitancy expressed by these patients. The study was based on two brief paper questionnaires completed in private by the general practitioner and the patient at the beginning of a medical appointment: one for the physician to evaluate on three quantitative and non-graduated visual scales (then analysed as a 0–100 scale) their patients' perceptions regarding vaccine safety, vaccine efficacy and 'being in favour of vaccination'; and one for the patient to express their perceptions for the same three axes using the same scales. Overall, 31 physicians participated in the study, with 540 physician-patient pairs being included. The physicians' evaluation of patient perceptions was more positive when the physician was male (vs female), when the patient was male (vs female) and when both were males (vs both females). The median differences (in absolute values) between the physician evaluations and the patient perceptions were between 9 and 11 (on the 0–100 scale) for the three axes (vaccine safety, vaccine efficacy and 'being in favour'). A correlation was observed between the physicians' evaluation and the patients' declaration (Kendall test: vaccine efficacy: tau = 0.199, p < 0.001; vaccine safety: tau = 0.234, p < 0.001; being in favour of vaccination: tau = 0.365, p < 0.001). Physicians correctly classified 83.4 % of the patients with high perceptions of vaccine safety and efficacy (>75/100 for both scales) but only 54.5 % of those with low perceptions (<75/100 for both scales). Physicians tend to correctly identify patients with the most favourable perceptions about vaccination but not those with the least favourable perceptions. [ABSTRACT FROM AUTHOR]

For pathogens which cause infections that present asymptomatically, evaluating vaccine efficacy (VE) against asymptomatic infection is important for understanding a vaccine's potential epidemiological impact. Regular testing for subclinical infections is a potentially valuable strategy but its success hinges on participant adherence and minimising false positives. This paper describes the implementation and adherence to weekly testing in a COVID-19 vaccine trial. COV002 was a phase 2/3 trial assessing the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2. Asymptomatic infections were detected using weekly self-administered swabs for RT-PCR testing. We analysed adherence using mixed-effects regression models and estimated the probability of true and false positive asymptomatic infections using estimates of adherence and testing characteristics. 356,551 tests were self-administered by 10,811 participants during the 13-month follow-up. Median adherence was 75.0% (IQR 42·6–90·9), which translated to a 74·5% (IQR 50·9–78·8) probability of detecting a positive asymptomatic infection during the swabbing period, and between 21 and 96 false positives during VE evaluation. The odds of returning a swab declined by 8% per week and further after testing positive and unblinding. Adherence was higher in older age groups, females and non-healthcare workers. The COV002 trial demonstrated the feasibility of running a long-term regular asymptomatic testing strategy. This information could be valuable for designing future phase III vaccine trials in which infection is an outcome. UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, AstraZeneca. [ABSTRACT FROM AUTHOR]

• Health Department reconsiders patient dismissal/nonacceptance for vaccine refusal. • Half of surveyed clinicians dismiss patients who refuse or delay pediatric vaccines. • Clinician attitudes on dismissal shift after educational public health intervention. • Findings suggest opportunity for interdisciplinary responses to vaccine refusal. In the United States, nearly half of pediatricians dismiss or refuse to accept families that withhold consent from the administration of childhood vaccines. Since 2016, the American Academy of Pediatrics has called patient dismissal in these cases "an acceptable option." Clinician dismissal and non-acceptance pose a problem to public health because they cluster under-vaccinated children in the practices that remain willing to treat such children, and they decrease access to routine care for children who cannot find practices willing to accept or retain them. This paper reports the emergence of a new consciousness about dismissal and non-acceptance policies in the leadership of a local health department (LHD) of a populous metropolitan county. To understand the prevalence and diversity of patient dismissal within Oakland County, Michigan and to measure shifts in clinicians' attitudes about dismissal following an educational intervention. A preliminary community survey was distributed to immunizing providers during April 2023 with 61 responses measuring the frequency and reasoning for dismissal policies. The results of the survey were used to inform a brief, evidence-backed educational intervention which was delivered in June 2023 to 82 participants from local pediatric medical offices. The initial survey was completed by 61 immunizing providers, representing an estimated 37% of vaccinating practices in the county. Half said their practice "always" or "sometimes" dismisses patients due to vaccine refusal. After the educational intervention, the proportion of participants who agreed/strongly agreed with the statement "I believe patient dismissal for vaccine refusal is a good choice for public health" decreased from 36% to 18%. The changes that we observed between the pre- and post-intervention surveys demonstrate the opportunity that exists for LHD leaders to enter the conversation around patient dismissal and nonacceptance and shed new light on this issue. [ABSTRACT FROM AUTHOR]

High-risk human papillomavirus (HPV) infections can progress to cervical cancer which is the fourth most common cancer in women globally. In Scotland, the incidence of cervical cancer has a strong socioeconomic deprivation gradient disproportionately affecting women from more deprived areas. An HPV vaccination programme was initiated in Scotland in 2008 targeting girls aged 12-13 years with a catch-up campaign running for the first three years for girls aged up to 18 years. The programme has evolved over the last 16 years with changes in the type of vaccine, dosing schedules and the extension of the programme to boys and gay, bisexual and other men who have sex with men. Vaccine uptake in Scotland has historically been high but has gradually decreased over time and disparities exist in women from more deprived areas of Scotland. The ability to link national immunisation and screening databases in Scotland has allowed direct monitoring of the impact of the HPV vaccine on virological and histological outcomes. Analyses of this linked data have demonstrated real-world evidence of high vaccine effectiveness against HPV infection, cervical disease, and cervical cancer with evidence of herd immunity in unvaccinated women. Continued monitoring is crucial to assess the duration of protection, the impact of vaccine and dosing schedules changes and the emergence of potential type replacement. With the World Health Organisation's aim to eliminate cervical cancer as a public health problem by the next century addressing the inequalities in cervical cancer incidence will be crucial. This will require targeted interventions for women most at risk of cervical cancer to ensure elimination is achieved timely for all women in Scotland., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kate Cuschieri reports a relationship with Hologic Inc. that includes: funding grants and travel reimbursement. Kate Cuschieri reports a relationship with Barinthus Biotherapeutics plc that includes: funding grants and non-financial support. Kate Cuschieri reports a relationship with EUROIMMUN Medizinische Labordiagnostika AG that includes: funding grants. Kate Cuschieri reports a relationship with GeneFirst that includes: funding grants. Kate Cuschieri reports a relationship with Hiantis that includes: funding grants. Kate Cuschieri reports a relationship with Seegene, Inc. that includes: funding grants. Kate Cuschieri reports a relationship with Roche that includes: funding grants. Kate Cuschieri reports a relationship with Daye that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: vaccines are complex products used in healthy populations. They should be carefully regulated, and benefits should clearly outweigh risks., Objectives: To describe the evidence used to support benefit-risk evaluations of vaccines centrally assessed by the European Medicines Agency (EMA), and to identify if real-world data (RWD) was used throughout the vaccine life cycle., Methods: Cohort study of vaccines approved in the European Union. Inclusion criteria comprised having ATC code J07 and being centrally approved between 2012 and 2022. We collected data from regulatory documents, study protocols, and, when necessary, from scientific publications. Vaccines were followed from initial approval up to March 2023., Results: We included 31 vaccines addressing 17 therapeutic areas. More than 390 studies were used in the process of initial marketing authorisation (MA) and monitoring, and 174 studies were listed in initial risk management plans. We also identified 93 studies in the EU PAS register. At MA, all vaccines had at least one pivotal trial and 27 vaccines had at least one supportive study. Most pivotal trials were randomized, double-blinded and active-controlled, with immunogenicity endpoints as primary outcome. RWD was used for extension of indications and monitoring of at least 4 vaccines, and the undertaking of RWE studies was foreseen in the RMP of at least 17 vaccines., Discussion: Our study revealed an important reliance on randomized controlled trials with individual-level randomization, and a significant focus on immunogenicity endpoints. The use of RWD in vaccine assessments so far has been restricted to COVID-19, and despite its challenges and limitations, we believe that efforts to expand adoption of RWE in continuous benefit-risk assessments should be made. We further highlight the need to enhance data transparency and reporting standards since heterogeneity among regulatory documents made it difficult to identify all the studies considered in vaccine evaluations., Competing Interests: Declaration of competing interest CEH is employed by the Copenhagen Centre for Regulatory Sciences (CORS), Department of Pharmacy, University of Copenhagen. CORS is a cross-faculty university-anchored institution involving various public (the Danish Medicines Agency, Copenhagen University) and private stakeholders (Novo Nordisk, Lundbeck, Ferring Pharmaceuticals, LEO Pharma) as well as patient organizations (Rare Diseases Denmark). The centre is purely devoted to the scientific aspects of the regulatory field and has a patient-oriented focus, and the research is not a company-specific product or directly company related. In the last three years, CORS and CEH have received funding from Novo Nordisk for projects not related to this study. LFW is a PhD student at CORS and his PhD fellowship is funded by a grant to CORS from Novo Nordisk A/S. However, the company was not involved in any aspect of the described work. DDG is also a PhD student at CORS, and she declares no competing interests. The authors declare no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Advisory Committee on Immunization Practices (ACIP) recommends early childhood vaccinations, but knowledge is limited about the magnitude and timing of vaccine delay for each recommended dose on a population level. We sought to characterize longitudinal patient-level patterns of early childhood vaccination schedule adherence., Methods: Using the Merative MarketScan Commercial Database (2009-2019), we identified commercially-insured infants who received at least one timely dose of a 2-month recommended vaccine. We categorized the number of recommended vaccines administered on the same date at 2, 4, 6, and 12-15 months of age (grace period: -7, +21 days). A Sankey diagram illustrated the number of vaccines received concomitantly during each age window and depicted transitions to different states over time (e.g., no vaccine delay to vaccine delay). For each vaccine dose, we estimated the cumulative incidence of receipt., Results: Among 1,239,364 eligible children, 28% of infants aged 4 months and 38% of infants aged 6 months did not receive timely, concomitant administration of all recommended vaccines. The number of timely vaccines received concomitantly and age at receipt varied most for doses recommended during the second year of life. Children with a previously delayed (versus timely) dose consistently experienced longer time to subsequent dose., Conclusions: National coverage improved over time for all recommended vaccine doses under study, most notably for measles, mumps, and rubella. However, many children do not receive vaccines on schedule. Interventions to maintain adherence to the recommended schedule are needed early in life., Competing Interests: Declaration of competing interest JGN and AMB have received investigator-initiated research contracts from Merck on topics unrelated to this article. At the time this research was conducted, LJM was an employee of and owned stock in NoviSci. She is now an employee and owns stock in Pfizer. No other authors have conflicts of interest to disclose. All authors attest they meet the ICMJE criteria for authorship. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anne Butler reports financial support and administrative support were provided by National Center for Advancing Translational Sciences. Anne Butler reports financial support was provided by National Center for Advancing Translational Sciences. Anne Butler reports a relationship with Merck & Co Inc. that includes: funding grants. Jason Newland reports a relationship with Merck & Co Inc. that includes: funding grants. Leah McGrath reports a relationship with Pfizer that includes: employment and equity or stocks. Leah McGrath reports a relationship with NoviSci that includes: employment and equity or stocks. JGN and AMB have received investigator-initiated research contracts from Merck on topics unrelated to this article. At the time this research was conducted, LJM was an employee of and owned stock in NoviSci. She is now an employee and owns stock in Pfizer. No other authors have conflicts of interest to disclose. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Major barriers to addressing SARS-CoV-2 vaccine hesitancy include limited knowledge of what causes delay/refusal of SARS-CoV-2 vaccination and limited ability to predict who will remain unvaccinated over significant time periods despite vaccine availability. The present study begins to address these barriers by developing a machine learning model that prospectively predicts who will persist in not vaccinating against SARS-CoV-2., Method: Unvaccinated individuals (n = 325) who completed a baseline survey were followed over the six-month period when vaccines against SARS-CoV-2 were first widely available (April-October 2021). A random forest model was used to predict who would remain unvaccinated against SARS-CoV-2 from their baseline measures, including demographic information (e.g., age), medical history (e.g., of influenza vaccination), Health-Belief Model constructs (e.g., perceived vaccine dangerousness), conspiracist ideation, and task-based metrics of vulnerability to conspiracist ideation (e.g., tendency toward illusory pattern perception)., Results: The resulting model significantly predicted vaccination status (AUC-PR = 0.77, 95%CI [0.56 0.90]). At the optimal probability threshold determined by the Generalized Threshold Shifting Protocol, the model was moderately precise (0.83) when identifying individuals who remained unvaccinated (n = 80), and had a very low rate (0.04) of false-positives (incorrectly suggesting that individuals remained unvaccinated). Permutational importance tests suggested that baseline SARS-CoV-2 vaccine intentions conveyed the most information about future SARS-CoV-2 vaccination status. Conspiracist ideation was the second most informative predictor, suggesting that misinformation influences vaccination behavior. Other important predictors included perceived vaccine dangerousness, as expected under the Health Belief Model, and influenza vaccination history., Conclusions: The model we developed can accurately and prospectively identify individuals who remain unvaccinated against SARS-CoV-2. It could therefore facilitate empirically-informed allocation of interventions that encourage vaccine uptake. The predictive value of conspiracist ideation, perceived vaccine dangerousness, and vaccine intentions in our model is consistent with potential causal relations between these variables and SARS-CoV-2 vaccine uptake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Pertussis vaccination in pregnancy has been introduced in an increasing number of countries to better protect infants against the disease in their first weeks of life. The optimal timing of pertussis vaccination in pregnancy is however still under debate., Methods: We systematically reviewed published literature on safety, immunogenicity and effectiveness of pertussis vaccination in pregnancy related to timing of vaccination. The search was conducted using PubMed, MEDLINE and Web of Science and yielded 1623 articles, thereof 777 duplicates. Screening resulted in the inclusion of 45 publications reporting on safety (n = 11), immunogenicity (n = 26) and/or effectiveness (n = 9). We also mapped pertussis recommendations in pregnancy by government institutions globally according to the recommended timing of vaccination., Results: Overall, the selected publications did not indicate increased safety concerns associated with timing of pertussis vaccination in pregnancy. Immunogenicity studies often suggested optimal protection at birth after early third trimester vaccination. Few studies investigated qualitative antibody characteristics, and none investigated antibody titers in breastmilk or cellular-mediated immunity related to timing of vaccination. Effectiveness studies showed decreased vaccine effectiveness of late third trimester pertussis vaccination compared to vaccination earlier in pregnancy. Worldwide, a general recommendation for pertussis vaccination in pregnancy was found for 58 countries, with as many as 22 different recommended timings registered., Conclusion: The timing of pertussis vaccination in pregnancy seems to impact immunogenicity and vaccine effectiveness, with optimal immune responses at birth suggested following early third trimester vaccination and reduced vaccine effectiveness of late third trimester pertussis vaccination suggested compared to vaccination earlier in pregnancy. However, inconsistent and lacking data are reflected in the divergent national recommendations for pertussis vaccination in pregnancy worldwide., Summary: Pertussis vaccination in pregnancy aims to protect infants in their first weeks of life. Our review suggests that immunogenicity and vaccine effectiveness are impacted by the timing of vaccination in pregnancy. National recommendations for pertussis vaccination in pregnancy vary widely worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This study aims to evaluate the safety of a new inactivated poliomyelitis vaccine (Sabin strains) (sIPV) for large-scale use in primary and booster immunizations, whether simultaneously administered with other vaccines or not and to explore the persistence of all vaccines at approximately six months after vaccination., Method: A total of 3200 infants were recruited into this study, including 2000 infants aged 2-3 months randomly assigned (1:1) into the "sIPV basic" or the "sIPV+DTaP" group for primary immunization of sIPV. Another 1200 children aged 18 months old and above were randomly assigned (2:2:1:1) into the "sIPV booster," "sIPV+HepA-I," "sIPV+MMR", or "sIPV+HepA-L" group for booster immunization of sIPV. Adverse events within 30 days of each vaccination dose in all participants were self-reported by guardians using a WeChat mini-program. Approximately 200 blood samples were collected at 5-7 months after the final vaccination to test for antibodies against poliovirus and other viruses., Results: 3198 participants in total were included in the safety study, including 1999 infants aged 2-3 months old and 1199 children aged 18-26 months old. For primary immunization, the incidence of adverse reactions in the "sIPV basic" and the "sIPV+DTaP" group were 3.19 and 6.21% (P = 0.001), respectively. For booster immunization, the incidences of adverse reaction for the "sIPV booster" group were 2.25%, while the incidence for the "sIPV +others" group in total was 2.50% (P = 0.788). Most adverse reactions were mild. Fever was the most common symptom in all groups. No vaccine-related serious adverse events (SAEs) were observed in this study. The seropositivity rates of antibodies in the "sIPV basic" and the "sIPV+DTaP" group were 92.31 and 100% against type 1 poliovirus (P = 0.031); 96.15% and 98.57% against type 2 poliovirus (P = 0.575); 98.08% and 91.43% against type 3 poliovirus (P = 0.237), respectively. Regarding booster vaccination with sIPV, whether co-administered with other vaccines or not, the seropositivity rates of antibodies against the three types of polioviruses were all 100%. Seropositivity rates of antibodies against hepatitis A, measles, mumps, and rubella were all no <77%, except for pertussis, which was <30%., Conclusion: sIPV demonstrated good safety and immune persistence for primary and booster vaccinations, whether administered singly or simultaneously. Antibodies against hepatitis A, measles, mumps and rubella were not disrupted by the co-vaccination. However, the seropositivity rates and geometric mean concentrations (GMCs) of antibodies against pertussis indicate the necessity for a booster dose., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Despite the emergence of SARS-CoV-2 variants and waning immunity after initial vaccination, data on antibody kinetics following booster doses, particularly those adapted to Omicron subvariants like XBB.1.5, remain limited. This study assesses the kinetics of anti-spike protein receptor-binding domain (S-RBD) IgG antibody titers post-booster vaccination in a Japanese population during the Omicron variant epidemic., Methods: A prospective cohort study was conducted in Bizen City, Japan, from November 2023 to January 2024. Participants included residents and workers aged ≥18 years, with at least three COVID-19 vaccinations. Antibody levels were measured from venous blood samples. The study analyzed 424 participants and 821 antibody measurements, adjusting for variables such as age, sex, underlying conditions, and prior infection status. Mixed-effects models were employed to describe the kinetics of log-transformed S-RBD antibody titers., Results: The study found that S-RBD antibody titers declined over time but increased with the number of booster vaccinations, particularly those adapted to Omicron and its subvariant XBB.1.5 (Pfizer-BioNTech Omicron-compatible: 0.156, 95%CI -0.032 to 0.344; Pfizer-BioNTech XBB-compatible: 0.226; 95%CI -0.051 to 0.504; Moderna Omicron-compatible: 0.279, 95%CI 0.012 to 0.546; and Moderna XBB-compatible: 0.338, 95%CI -0.052 to 0.728). Previously infected individuals maintained higher antibody titers, which declined more gradually compared to uninfected individuals (coefficient for interaction with time 0.006; 95%CI 0.001 to 0.011). Sensitivity analyses using Generalized Estimating Equations and interval-censored random intercept model confirmed the robustness of these findings., Conclusions: The study provides specific data on antibody kinetics post-booster vaccination, including the XBB.1.5-adapted vaccine, in a highly vaccinated Japanese population. The results highlight the importance of considering individual demographics and prior infection history in optimizing vaccination strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takashi Yorifuji reports financial support was provided by Bizen city. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Our study aims to investigate the dynamics of conventional memory T cells (Tconv) and regulatory memory T cells (Treg) following activation, and to explore potential differences between these two cell types. To achieve this, we developed advanced statistical mixed models based on mathematical models of ordinary differential equations (ODE), which allowed us to transform post-vaccination immunological processes into mathematical formulas. These models were applied to in-house data from a de novo Hepatitis B vaccination trial. By accounting for inter- and intra-individual variability, our models provided good fits for both antigen-specific Tconv and Treg cells, overcoming the challenge of studying these complex processes. Our modeling approach provided a deeper understanding of the immunological processes underlying T cell development after vaccination. Specifically, our analysis revealed several important findings regarding the dynamics of Tconv and Treg cells, as well as their relationship to seropositivity for Herpes Simplex Virus Type 1 (HSV-1) and Epstein-Barr Virus (EBV), and the dynamics of antibody response to vaccination. Firstly, our modeling indicated that Tconv dynamics suggest the existence of two T cell types, in contrast to Treg dynamics where only one T cell type is predicted. Secondly, we found that individuals who converted to a positive antibody response to the vaccine earlier had lower decay rates for both Tregs and Tconv cells, which may have important implications for the development of more effective vaccination strategies. Additionally, our modeling showed that HSV-1 seropositivity negatively influenced Tconv cell expansion after the second vaccination, while EBV seropositivity was associated with higher Treg expansion rates after vaccination. Overall, this study provides a critical foundation for understanding the dynamic processes underlying T cell development after vaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benson Ogunjimi reports financial support was provided by European Research Council. Benson Ogunjimi reports financial support was provided by Research Foundation Flanders. Philippe Beutels reports financial support was provided by University of Antwerp. Pierre Van Damme reports financial support was provided by University of Antwerp. CONFLICT OF INTEREST STATEMENT: BO declares that the University Hospital Antwerpen and the University of Antwerp have received investigator-initiated grants from Abbvie, Pfizer and Roche. BO is a shareholder and member of the board of ImmuneWatch BV. NH declares that the Universities of Antwerp and Hasselt have received funding for advisory boards and research projects of MSD, GSK, JnJ, Pfizer and the European Commission’s IMI programme outside the proposed work. NH has not received any personal remuneration. PB declares the University of Antwerp received compensation for unrelated consultancy for Pfizer in 2019, research grants from MSD and Pfizer, and the European Commission’s IMI programme. PB has not received any personal remuneration. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. KL is a shareholder and member of the board of ImmuneWatch BV. PM is a shareholder, employee and member of the board of ImmuneWatch BV. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Given their vulnerable health status and resource constraints, the perspectives of women with criminal-legal involvement (WCLI) are important but not usually represented in the literature on vaccine interest and vaccine hesitancy. This study aims to examine how the COVID-19 pandemic and vaccine affected the influenza vaccine uptake among WCLI., Methods: A cross-sectional secondary analysis was conducted using data collected from the Tri-City study, which followed WCLI in three U.S. cities from 2019 to 2023. We mapped the distribution of influenza vaccine uptake in 2019-2023 and developed a composite outcome that reflected participants' patterns of Y/N to influenza vaccine, which were categorized into four groups: Influenza Vaccine Supportive, Influenza Vaccine Adaptive, Influenza Vaccine Discontinued, and Influenza Vaccine Resistant., Results: Out of 507 people: 23.7% were Supportive, 8.5% Adaptive, 15.2% Discontinued and 38.3% Resistant. People who received the COVID vaccine had significantly lower odds of being identified as Discontinued (OR = 0.42, 95%CI = 0.20-0.87, p = .020) and Resistant (OR = 0.23, 95%CI = 0.13-0.43, p < .001), compared to the Supportive group. Mistrust toward COVID-19-related information was a significant independent predictor of being Adaptive (OR = 1.59, 95%CI = 1.08-2.35, p = .019), Discontinued (OR = 1.61, 95%CI = 1.15-2.25, p = .006), and Resistant (OR = 1.54, 95%CI = 1.19-2.00, p < .001) relative to Supportive., Conclusions: Vaccine hesitancy poses significant challenges to public health efforts, with apparent dampening effect across vaccines. Public health messaging and clinical interactions informed by best practices in communication tailored to the lived experience of all people, including women with criminal-legal system involvement, will be necessary to inform future interventions aimed at increasing vaccine uptake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The association between maternal COVID-19 vaccination in pregnancy and factors such as high risk for severe COVID-19, pre-existing asthma, prior adverse reproductive history, or paternal COVID-19 vaccination during pregnancy, remains unclear. The aim of this study is two-fold: (i) to describe uptake of COVID-19 vaccine during pregnancy by maternal risk for severe COVID-19 and asthma, and (ii) to comprehensively examine individual and familial factors associated with vaccine uptake during pregnancy in Norway. Based on nation-wide registry-linkage data in Norway, we included 101,659 deliveries with gestational length ≥12 weeks, in 2021-2022. Our outcome measure was uptake of at least one dose of mRNA COVID-19 vaccine during pregnancy, using a narrow (first ever dose) and broad (any dose) definition. We fit univariate and multivariate modified Poisson regression models, clustered by county of residency and adjusted for calendar time, to estimate risk ratios (RR) with 95 % Confidence Intervals (CIs). Gestational uptake of any COVID-19 vaccine dose increased from <1 % before mid Aug-2021, to 38.8 % in the rest of 2021, and 48.9 % in 2022. Only 28.8 % and 33.9 % pregnant individuals with high risk for severe COVID-19 or asthma, respectively, received at least one COVID-19 vaccine dose. Paternal COVID-19 vaccination was strongly associated with greater vaccine uptake by pregnant individuals (adjusted RR: 7.2, 95 % CI: 6.8-7.5). Maternal SARS-CoV-2 infection pre-pregnancy (adjusted RR: 0.31, 95 % CI: 0.26, 0.37), familial and individual migrant status were associated with a considerable decreased likelihood of vaccine uptake in pregnancy. History of miscarriage or pregnancy with congenital anomaly were not associated with vaccine uptake. Despite rising COVID-19 vaccine rates in pregnancy, uptake remained low for high-risk individuals. Paternal vaccination, pre-pregnancy infection, migration status, and maternal citizenship were strongly associated with prenatal vaccine uptake. This knowledge can inform tailoring of future vaccination campaigns., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Angela Lupattelli reports financial support was provided by European Union. This work is part of the VERDI project (101045989) which is funded by the European Union. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Health Canada recently authorized the RSVpreF pregnancy vaccine and nirsevimab to protect infants against respiratory syncytial virus (RSV) disease., Objective: Assess the cost-effectiveness of RSVpreF and nirsevimab programs in preventing RSV disease in infants, compared to a palivizumab program., Methods: We used a static cohort model of a Canadian birth cohort during their first RSV season to estimate sequential incremental cost-effectiveness ratios (ICERs) in 2023 Canadian dollars per quality-adjusted life year (QALY) for nine strategies implemented over a one-year time period, from the health system and societal perspectives. Sensitivity and scenario analyses were conducted to explore the impact of uncertainties on the results., Results: All-infants nirsevimab programs averted more RSV-related outcomes than year-round RSVpreF programs, with the most RSV cases averted in a seasonal nirsevimab program with catch-up. Assuming list prices for these immunizing agents, all-infants nirsevimab and year-round RSVpreF programs were never cost-effective, with ICERs far exceeding commonly used cost-effectiveness thresholds. Seasonal nirsevimab with catch-up for infants born outside the RSV season was a cost-effective program if prioritized for infants at moderate/high-risk (ICER <$28,000 per QALY) or those living in settings with higher RSV burden and healthcare costs, such as remote communities where transport would be complex (ICER of $5700 per QALY). Using a $50,000 per QALY threshold, an all-infants nirsevimab program could be optimal if nirsevimab is priced at <$110-190 per dose. A year-round RSVpreF for all pregnant women and pregnant people plus nirsevimab for infants at high-risk was optimal if nirsevimab is priced at >$110-190 per dose and RSVpreF priced at <$60-125 per dose., Interpretation: Prophylactic interventions can substantially reduce RSV disease in infants, and more focused nirsevimab programs are the most cost-effective option at current product prices., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ellen Rafferty reports a relationship with Natural Sciences and Engineering Research Council of Canada that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Objective: Respiratory syncytial virus (RSV) causes significant lower respiratory tract infections (LRTIs) in infants and young children. Current prevention targets those under 2 years. This study aims to evaluate RSV patterns and severity in children older than 2 years and to explore the potential extension of preventive strategies to this demographic group., Methods: An observational retrospective study at Meyer Children's Hospital (from October 2019 to March 2023) analyzed data from patients between 28 days and 18 years of age with RSV infection. Severity indicators and patient characteristics were compared between two age groups: under 2 years and 2 years and above., Results: 584 infants and young children were hospitalized due to RSV infection. Epidemic seasons saw a rise in hospitalizations among children older than 2 years. Older children had higher comorbidity (41% versus 9% p=0.000) and prematurity (26% versus 14% p = 0.001) rates than those under 2 years., Conclusion: The study highlights the increased risk of severe RSV LRTIs in children older than 2 years and with prematurity or comorbidities, overlooked by current preventive measures. Prospective studies and cost-effectiveness analyses are needed to determine the necessity of targeted immunization for older children with specific risk factors, aiming to reduce RSV-related morbidity and mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Influenza seasons occur annually, building immune history for individuals, but the influence of this history on subsequent influenza vaccine protection remains unclear. We extracted data from an animal trial to study its potential impact. The trial involved 80 ferrets, each receiving either one type of infection or a placebo before vaccination. We quantified the vaccine protection by evaluating hemagglutination inhibition (HAI) antibody titer responses. We tested whether hosts with different infection histories exhibited similar level of responses when receiving the same vaccine for all homologous and heterologous outcomes. We observed that different pre-existing immunities were generally beneficial to vaccine induced responses, but varied in magnitude. Without pre-immunity, post-vaccination HAI titers after the 1st dose of the vaccine were less likely to be above 1:40, and a booster shot was needed. Our study suggests that pre-existing immunity may strengthen and extend the homologous and heterologous vaccine responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted routine childhood vaccination worldwide, especially at the beginning of the pandemic. After the emergence of variants of concern, particularly the Omicron variants, the number of COVID-19 cases significantly increased, especially in children. However, the impact of the Omicron variants on routine childhood vaccination is unknown., Methods: This retrospective observational study collected data on vaccines included in the Japanese national immunization program (NIP) of children 15 years or younger between 2016 and 2022 in Niigata, Japan. During the study period, hepatitis B virus vaccine and rotavirus vaccines were introduced to the NIP in October 2016 and October 2020, respectively. The monthly number of vaccine doses per eligible child population between 2020 and 2022 (pandemic period) was compared to the average number of vaccine doses in the corresponding month between 2016 and 2019 (pre-pandemic period). The effect of 8 surges of COVID-19 patients on trends in routine childhood vaccination was also analyzed., Results: The numbers of doses during the pre-Omicron pandemic period were comparable to the values administered before the pandemic. However, after the emergence of the Omicron variants, and especially after the surge of Omicron variant BA.5 in 2022, the number of vaccine doses declined. The decline was notable in second doses of MR vaccine at age 5-6 years by - 9.6 % and diphtheria-tetanus vaccine at ages 11-12 years by - 14.1 %., Conclusions: Routine childhood immunization was significantly affected by the emergence of the Omicron variants most likely due to the facts that more candidates and their guardians contracted COVID-19, or were required isolation for close contacts. The findings highlight the importance of continued monitoring to maintain high coverage of routine childhood immunizations for controlling vaccine preventable diseases. A follow-up study should investigate changes in the number of declined vaccine doses during Omicron variant predominance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Yuta Aizawa reports a relationship with Merck & Co Inc that includes: speaking and lecture fees. Akihiko Saitoh reports a relationship with Merck & Co Inc that includes: speaking and lecture fees. Akihiko Saitoh reports a relationship with Pfizer Inc that includes: speaking and lecture fees. Akihiko Saitoh reports a relationship with Mitsubishi Tanabe Pharma Corporation that includes: speaking and lecture fees. Akihiko Saitoh reports a relationship with Osaka University Research Institute for Microbial Diseases that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In recent years, notified pertussis cases have been increasingly documented in China. It raised a new public health concern of potential optimization in immunization strategy. This study was aimed to determine the cost-effectiveness of different immunization strategies against pertussis-containing vaccines for 6-year-old pre-school children in Shanghai., Methods: A Markov-decision tree model was applied to evaluate two pertussis immunization strategies for 6-year-old pre-school children as following: (1) 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster vaccinated at 6 years of age, and (2) no booster at 6 years of age regimen. Primary outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-utility ratios (ICUR). Sensitivity analyses were performed. The analysis was conducted over a study period of 14 years from a societal perspective., Results: Compared to no booster immunization strategy, administering 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster at 6 years of age, resulted in an average cost reduction of CNY 814.16 (USD 116) per individual, an increase in QALYs by 0.00066, and a rise in per capita net monetary benefit (NMB) by CNY 933.51 (USD 132). The total costs over the study period were reduced by CNY 160.59 million (USD 23 million), utility increased by 130.49 QALYs, and NMB increased by CNY 184.14 million (USD 26 million)., Conclusions: Implementing acellular pertussis booster immunization for 6-year-old pre-school children in Shanghai emerges as a cost-saving immunization strategy, with both cost savings and utility gains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Influenza vaccines are effective in decreasing hospitalizations and mortality related to influenza and its complications. However, the Vaccine Coverage Rate of influenza remains low and multifaceted efforts are required to improve it. The aim of this study was to assess the impact on influenza vaccine perception using a digital tool among outpatients and health care workers (HCWs)., Methods: A study was performed among outpatients and the HCWs of 23 hospital departments from 4 hospitals affiliated to Lyon university Hospitals (France), between October 2022 and February 2023. By scanning QR (Quick Response) codes, displayed on posters for patients, their companions, as well as in the letters sent to HCWs, users accessed anonymously to a web-application (ELEFIGHT®), which provided information on influenza and invited them to initiate a discussion on influenza prevention with their physicians during the consultation. Patients were also invited to complete a questionnaire regarding their perception of influenza vaccination before and after reading the information on ELEFIGHT®. The retention rate (RR = proportion of people who remain on the page for >2 s), the conversion rate (CR = proportion of people who click on the "Call-To-Action" button) and the absolute variation (difference in the perception before/after) and relative variation (absolute change as a percentage of the initial perception) in perception regarding influenza vaccination before and after consulting the application were calculated., Results: 3791 scans were performed by 3298 patients and/or their companions with a RR of 52% and a CR of 55.1% and 253 scans by 221 HCWs with a RR of 71.2% and a CR of 115.3%. Participants spent an average of 47 s on the application. The questionnaire on influenza vaccination perception was completed by 1533 participants (46.5%); 1390 (90.7%) maintained the same position (neutral, favorable or unfavorable) on this vaccination before and after consulting the application. The relative variations in favor of vaccination were + 7.2% (unfavorable then favorable) and + 19.8% (neutral then favorable)., Conclusion: This study suggests that a facilitated direct access to medical information through QR codes disseminated in health settings can help nudge people to foster their awareness of influenza and its prevention. Future deployments in a similar context or to other populations could be envisaged. Other vaccine-preventable and/or chronic diseases could also be the target of similar projects as part of public health programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nagham Khanafer, Florence Ader, Frédéric Berard, Françoise Bouhour, Roland Chapurlat, Sybil Charriere, Cyrille Confavreux, Gilles Devouassoux, Emmanuel Disse, Jean-Pierre Fauvel, Denis Fouque, Herve Ghesquieres, Sophie Hyvert, Anne Jolivot, Gilles Leboucher, Catherine Lombard, Géraldine Martin-Gaujard, Jean-Francois Mornex, Marc Nicolino, Nathalie Obadia, Gérald Raverot, Philippe Reix, Alain Ruffion, Pascal Seve, Eric Truy, Fabien Zoulim and Philippe Vanhems have no conflicts of interest related to this study to declare. Catherine Planckaert, Rym Bouhalila, Camille Mena and Nadège Trehet Mandel have been mandated and paid by the HCL. Sylvain Oudot, Margot Maligeay, Joséphine Clamens and Marie-Pierre Ayala are employed by Sanofi., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To identify sociodemographic factors associated with HPV vaccine uptake in a universal, in-school HPV vaccination program, among grade 6 and 9 students in the regional health authority of Vancouver Coastal Health (VCH), British Columbia (BC), Canada during the 2021/22 school year. VCH operates within the southwest corner of the province of BC serving a mix of urban and rural regions. HPV vaccine is offered in school to all grade 6 students using a two-dose series, with catch up immunizations offered to students in grade 9., Methods: We conducted a cross-sectional study of grade 6 and 9 students enrolled in VCH schools for the 2021/22 school year, who also resided within the VCH region. We modelled the associations between sociodemographic explanatory variables (individual-level and group-level) and fully vaccinated outcome using a cross-classified (non-nested) multilevel model., Results: Among the 17,939 students eligible, 74 % were fully vaccinated for HPV. Immunization coverage was associated with grade, geographic area of residence, school category, social and material deprivation. We demonstrated that grade modified the association between material deprivation and being fully vaccinated. Grade 9 students, including those residing in more materially deprived neighbourhoods, had substantially higher odds (OR 2.01 [95 % CI 1.08, 3.75]) of being fully vaccinated relative to grade 6 students in the least materially deprived neighbourhoods., Conclusions: Though publicly funded HPV vaccine is offered to all students in grade 6 and 9, in a space that maximizes programmatic access, sociodemographic factors associated with under-immunized populations were identified. This information can be leveraged for strategic targeting of resources to underimmunized schools or students to mitigate impacts. The repeat offering of HPV vaccine in an older grade (grade 9 in BC) is a key programmatic strategy to reach under-immunized populations and should be complemented by other creative approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Currently, there is limited understanding of the specific humoral immune response in BA.5-infected hemodialysis patients (BA.5-CHDPs) with previous COVID-19 vaccination. Additionally, the relevant risk factors for reinfection with XBB variants in BA.5-CHDPs have yet to be elucidated., Method: A total of 178 BA.5-CHDPs were enrolled in this study among 53 patients who had previous vaccination. To compare hemodialysis patients in both unvaccinated and vaccinated for their immune response to the BA.5 subtype infection, we assessed serum levels of anti-ancestral-S1-IgG, anti-BA.5-receptor binding domain (RBD)-IgG, and anti-XBB.1.16-RBD-IgG using enzyme-linked immunosorbent assay, the neutralizing antibody titer against BA.5 and XBB.1.16 was determined using pseudovirus neutralization assays. Univariate and multivariate binary logistic regression analyses were conducted to identify factors associated with severe infection, the magnitude of specific humoral immunity and susceptibility to XBB variants reinfection., Result: Our findings indicate that BA.5-CHDPs with full or booster vaccinations have higher levels of anti-ancestral-S1-IgG than unvaccinated individuals. However, levels of anti-BA.5-RBD-IgG and anti-XBB.1.16-RBD-IgG are much lower. Booster-vaccinated BA.5-CHDPs have significantly higher levels of BA.5 and XBB.1.16 specific antibodies and neutralizing antibodies than unvaccinated patients. Low globulin levels and shorter hemodialysis duration are independent risk factors for XBB reinfection in BA.5-CHDPs., Conclusion: Although XBB.1.16 specific neutralizing antibody levels were low in BA.5-CHDPs, these levels cannot predict the risk of reinfection; other potential risk factors need to be investigated in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Globally, there has been a commitment to produce and distribute a vaccine within 100 days of the next pandemic. This 100-day target will place pressure on countries to make swift decisions on how to optimise vaccine delivery. We used data from the COVID-19 pandemic to inform mathematical modelling of future pandemics in Indonesia for a wide range of pandemic characteristics. We explored the benefits of vaccination programs with different start dates, rollout capacity, and age-specific prioritisation within a year of the detection of a novel pathogen. Early vaccine availability, public uptake of vaccines, and capacity for consistent vaccine delivery were the key factors influencing vaccine benefit. Monitoring age-specific severity will be essential for optimising vaccine benefit. Our study complements existing pathogen-specific pandemic preparedness plans and contributes a tool for the rapid assessment of future threats in Indonesia and similar middle-income countries., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Amblyomma sculptum is widely distributed in Brazil and is the main vector of Rickettsia rickettsii, the causative agent of the Brazilian spotted fever (BSF). Tick gut proteins play an essential role in blood feeding, digestion, and protection of gut epithelium. Therefore, many of these were investigated as potential vaccine targets for tick-control strategies. The present study aimed to select transcripts corresponding to putative immunogenic proteins in the A. sculptum gut epithelial membrane, produce recombinant proteins and evaluate them as antigens against A. sculptum infestations. Three gut proteins - AsMucin, AsAPP, and AsLAMP - and a chimeric protein (rAsChimera) based on 22 peptides containing putative B cell epitopes from seven different gut proteins were evaluated as anti-A. sculptum antigens. Mice immunizations revealed that all recombinant targets elicited humoral response with significantly increased IgG levels compared to controls. For rAsChimera, IgG levels remained significantly higher than controls up to 75 days after the end of the immunization. Challenge trials revealed that vaccination with the chimeric protein was the most effective against A. sculptum, inducing 100 % nymph mortality and reaching 80.8 % efficacy against females. The other three proteins did not induce relevant protection, as AsAPP had only 26.6 % efficacy, whereas AsMucin and AsLAMP induced no protection. These data indicate that targeting gut protein immunogenic regions may be an effective strategy for a vaccine formulation againstA. sculptum., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ricardo Nascimento Araujo has patent #BR 10 2019 018609 7 pending to INPI- Instituto Nacional de Propriedade Intelectual. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Transmission-blocking vaccines interrupting malaria transmission within mosquitoes represent an ideal public health tool to eliminate malaria at the population level. Plasmodium falciparum and P. vivax account for more than 90% of the global malaria burden, co-endemic in many regions of the world. P25 and P48/45 are two leading candidates for both species and have shown promising transmission-blocking activity in preclinical and clinical studies. However, neither of these target antigens as individual vaccines has induced complete transmission inhibition in mosquitoes. In this study, we assessed immunogenicity of combination vaccines based on P25 and P48/45 using a DNA vaccine platform to broaden vaccine specificity against P. falciparum and P. vivax. Individual DNA vaccines encoding Pvs25, Pfs25, Pvs48/45 and Pfs48/45, as well as various combinations including (Pvs25 + Pvs48/45), (Pfs25 + Pfs48/45), (Pvs25 + Pfs25), and (Pvs48/45 + Pfs48/45), were evaluated in mice using in vivo electroporation. Potent antibody responses were induced in mice immunized with individual and combination DNA vaccines, and specific antibody responses were not compromised when combinations of DNA vaccines were evaluated against individual DNA vaccines. The anti-Pvs25 IgG from individual and combination groups revealed concentration-dependent transmission-reducing activity (TRA) in direct membrane feeding assays (DMFA) using blood from P. vivax-infected donors in Brazil and independently in ex vivo MFA using Pvs25-transgenic P. berghei. Similarly, anti-Pfs25 and anti-Pfs48/45 IgGs from mice immunized with Pfs25 and Pfs48/45 DNA vaccines individually and in various combinations revealed antibody dose-dependent TRA in standard membrane feeding assays (SMFA) using culture-derived P. falciparum gametocytes. However, antibodies induced by immunization with Pvs48/45 DNA vaccines were ineffective in DMFA and require further vaccine construct optimization, considering the possibility of induction of both transmission-blocking and transmission-enhancing antibodies revealed by competition ELISA. These studies provide a rationale for combining multiple antigens to simultaneously target transmission of malaria caused by P. falciparum and P. vivax., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Healthcare workers (HCWs) are recommended to receive at least three spike-antigen exposures to generate basic immunity and to mediate herd protection of vulnerable patients. So far, less attention has been put on the cellular immune response induced by homologous (three BTN162b2mRNA doses) or heterologous (mRNA-1273 as third dose building on two BTN162bmRNA doses) and the immunological impact of breakthrough infections (BTIs). Therefore, in 356 vaccinated HCWs with or without BTIs the Anti-SARS-CoV-2-Spike-IgG concentrations and avidities and B- and T-cell-reactivity against SARS-CoV-2-Spike-S1- and Nucleocapsid-antigens were assessed with Interferon-gamma-ELISpot and by flow-cytometry. HCWs who had hybrid immunity due to BTIs exhibited strong T-cell-reactivity against the Spike-S1-antigen. A lasso regression model revealed a significant reduction in T-cell immune responses among smokers (p < 0.0001), with less significant impact observed for age, sex, heterologous vaccination, body-mass-index, Anti-Nucleocapsid T-cell reactivity, days since last COVID-19-immunization, and Anti-SARS-CoV-2-Spike-IgG. Although subgroup analysis revealed higher Anti-SARS-CoV-2-Spike-IgG after heterologous vaccination, similar cellular reactivity and percentages of Spike-reactive T- and B-cells were found between homologous and heterologous vaccination. Anti-SARS-CoV-2-Spike-IgG concentrations and avidity significantly correlated with activated T-cells. CD4 + and CD8 + responses correlated with each other. A strong long-term cellular immune response should be considered as baseline for recommendations of booster doses in HCWs with prioritization of smokers. HCWs presented significant T-cellular reactivity towards Spike-S1-antigen with particularly strong responses in hybrid immunized HCWs who had BTIs. HCWs without BTI presented similar percentages of Spike-specific B- and T-cells between homologous or heterologous vaccination indicating similar immunogenicity for both mRNA vaccines, BNT162b2mRNA and mRNA-1273., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Martina Prelog received honoraria for presentations at scientific meetings from Abbvie, BioNTech, Chugai-Roche, Doctorflix, GSK, Esanum, Janssen, Novartis, Moderna, MSD, Pfizer, Sanofi and SOBI, received honoraria for advisory boards from Abbvie, BioNTech, GSK, Janssen, Moderna, Novartis, and Pfizer , received travel scholarships from Chugai-Roche, GSK, Novartis and Pfizer, received financial support for conduction of investigator-initiated research from Baxter, Chugai-Roche, Galapagos,  GSK, Moderna, Novartis, MSD, Pfizer and SOBI; Martina Prelog declares to have no conflict of interest regarding the manuscript.  Manuel Krone receives honoraria from GSK and Pfizer outside the submitted work. All other authors declare no potential conflicts of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

At present, mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being administered on a global scale. While the efficacy of mRNA vaccines has been demonstrated, several unknowns remains. For example, as the number of booster vaccinations increases, there are uncertainties regarding how long effects of a vaccine will last and how much individual variability exists. In this study, to predict the duration of vaccine efficacy, we modeled the kinetics of antibody levels for each SARS-CoV-2 vaccination dose, incorporating predictive intervals to estimate the duration of vaccine efficacy and to account for variability among individuals. A total of 3,059 serum samples from 1,346 participants were assayed to quantify IgG antibodies specific for the S1 subunit of the S protein (anti-S1 IgG) and neutralizing antibody activities against SARS-CoV-2. A power law model was used to simulate the decay of antibody titers following vaccination, and models were constructed to assess antibody level kinetics after the second, third, fourth, and fifth vaccinations. The models assumed that booster vaccinations would significantly reduce the decline in anti-S antibody and neutralizing antibody levels, resulting in levels being maintained for a longer period. No significant differences in the decay rate of antibody levels were observed among age groups, yet the peak titers of antibody levels were significantly higher in the ≤ 39 age group than in the ≥ 60 age group following the second vaccination; these differences were not observed after the third and fourth vaccinations. The modeling of antibody level kinetics after vaccination is considered to be useful for understanding the immune status of mRNA vaccine recipients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The reported number of pertussis cases declined after the implementation of COVID-19 prevention and control measures, however, the burden of pertussis among adults in China remains largely unknown. Additionally, the waning of natural antibody level has also rarely been assessed., Methods: A total of 762 healthcare workers (HCWs) who had underwent the health examinations in 2021 and 2022 were included. Serum anti-PT IgG and IgA levels were determined by ELISA. Recent B. pertussis infection was defined as anti-PT IgG ≥100 IU/ml and/or anti-PT IgA ≥10 IU/ml., Results: In 2021, the seroprevalence of recent B. pertussis infection was 10.1 %, and those HCWs in outpatient department had a higher percentage (18.6 %), and geometric mean concentration (GMC) (6.3 IU/ml) than those in other departments. This seroprevalence decreased to 2.4 % in 2022, although the difference remained significant. In the 77 subjects with recent B. pertussis infection in 2021, anti-PT IgG was undetectable in 18 cases the following year. Majority (68/76) of the subjects with anti-PT IgA ≥10 IU/ml in 2021 no longer had detected this antibody in 2022. Among 95 pertussis cases, approximately 60.0 % of cases reported no history of cough. Among those with a documented cough history, 36 cases with suspected pertussis courses who had never been diagnosed. Prolonged cough with nocturnal exacerbation (29/38) was the most commonly reported clinical symptom, and whoop was confirmed in six cases. Uroclepsia and syncopes during the cough attacks were reported by three and one subjects, respectively. One case presented with subconjunctival hemorrhage and tensionic purpura during the course., Conclusions: The results suggested a high prevalence of B. pertussis infection among HCWs. The presence of unrecognized adult pertussis cases and the rapid waning of antibody indicate the need to improve clinical management for suspected pertussis in adults, and to updated immunization schedule after childhood program., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: School-based immunization programs offer an accessible route to routine vaccines for students. During the COVID-19 pandemic, school closures to comply with public health measures had a drastic effect on school-based immunization program delivery and associated vaccine uptake. We sought to integrate findings from a mixed methods study to co-develop evidence-based and theory-informed recommendations with a diverse group of stakeholders (i.e., decision makers, healthcare providers, school staff, parents and adolescent students) to address barriers to new and existing school-based immunization programs., Methods: Findings from a mixed methods study were integrated using a joint display and narrative summary. These findings were mapped through the Behaviour Change Wheel, a series of tools designed to facilitate the development of behaviour change interventions. Draft recommendations were provided to previous mixed methods study participants who consented to participating in future phases of the research study (n = 26). Feedback was captured using a Likert-scale survey of acceptability, practicality, effectiveness, affordability, safety and equity (APEASE) criteria, with feedback and additional insights captured using open-ended textboxes. Data was used to revise and finalize recommendations., Results: Applying the Behaviour Change Wheel, we drafted 26 evidence-based, theory-informed recommendations to address barriers to school-based immunization programs. Participants (n = 16) provided feedback, with half of the recommendations scoring 80% or higher across all six APEASE criteria. The remaining 13 recommendations received a moderate score across one or more criteria. Stakeholders identified a high level of interest in expanding the use of e-consent forms, expanding programming to offer a meningitis B vaccine, and recommendations to ease student anxiety., Conclusion: We co-developed a range of recommendations to improve school-based immunization programs with stakeholders using data generated from a mixed methods study. Implementation of any single or combination of recommendations will need to be tailored to local clinic procedures, school system and health system resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Childhood vaccine uptake in the United Kingdom (UK) is sub-optimal leading to outbreaks of preventable diseases. We aimed to explore UK parents' perspectives on why some children are unvaccinated or vaccinated late., Methods: We undertook a mixed-methods, co-production study involving a survey using a questionnaire followed by focus groups. We partnered with The Mosaic Community Trust (Mosaic) who are based in a more deprived, ethnically diverse, low vaccine uptake area of London. Targeted recruitment to complete the questionnaire (either on paper or online) was done through Mosaic, community networks and social media promotion. We collected demographic data alongside parents' views on routine childhood vaccination, their vaccine decisions, and experiences of accessing childhood vaccine appointments We report descriptive findings from the questionnaire and thematic analysis of free-text questionnaire answers and focus groups guided by the COM-B model of Capability, Opportunity, and Motivation., Results: Between June-October 2022, 518 parents were surveyed of whom 25% (n = 130), were from ethnic minorities (13%, n = 68-unknown ethnicity). In 2023 we held four focus groups with 22 parents (10 from ethnic minorities). Only 15% (n = 78) parents had delayed or refused a vaccine for their child. A quarter of parents felt they had not been given enough information nor an opportunity to ask questions before their children's vaccinations. Inconsistent reminders and difficulties booking or attending appointments impacted vaccine uptake with negative experiences influencing future vaccine decisions. Parents had mixed views on vaccinations being given in different locations and wanted trusted health professionals to vaccinate their children., Conclusion: To reverse declining vaccine uptake and prevent future outbreaks it needs to be easier for UK parents to speak to health professionals to answer their childhood vaccine questions, alongside simplified booking systems and easier access to routine childhood vaccine appointments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Helen Skirrow reports financial support was provided by National Institute for Health and Care Research. Celine Lewis reports financial support was provided by National Institute for Health and Care Research. Sonia Saxena reports financial support was provided by National Institute for Health and Care Research. Kim Foley reports financial support was provided by National Institute for Health and Care Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan., Methods: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates., Results: Of the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively., Conclusion: Replacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Measles vaccination has greatly reduced the disease burden worldwide, but challenges remain due to variations in vaccine effectiveness across age groups. This study aimed to assess the serological profile of measles antibodies across different age groups, evaluate the impact of maternal immunity on antibody levels in infants under 12 months, and assess measles immunity in vaccinated individuals., Material and Methods: This cross-sectional study was conducted from June 2022 to January 2023 at the Children's Medical Center, a referral hospital in Iran. Serum samples were tested for measles-specific IgG and IgM antibodies using a commercial enzyme-linked immunosorbent assay (ELSA). An avidity assay was performed to assess measles virus-specific IgG antibodies on the samples that were positive and borderline for the measles IgG ELISA., Results: The study included 969 participants across various age groups. Among them, 23% (221 out of 953) tested positive for measles IgM ELISA, and 52% (504 out of 969) for measles IgG ELISA. Regarding the avidity assay for measles virus-specific IgG, the majority (418 out of 573, 73%) showed high-avidity antibodies. Measles-specific IgG levels varied significantly across different age groups, with infants below 6 months old showing a mean IgG level of 477 mIU/mL, declining to 230 mIU/mL between 6 and 12 months, and increasing significantly to 683 mIU/mL in the 12 to 18 month age group, reaching a peak at 938 mIU/mL among children aged 18-72 months., Conclusion: The increasing IgM positivity among young Iranians suggests a rising risk of measles outbreaks, possibly due to vaccination gaps. Inadequate antibody levels in infants raise concerns about vaccination effectiveness. Considering declining maternal antibodies, vaccinating infants at 6-9 months could be beneficial. Boosters for adolescents and women may further mitigate outbreak risks., Competing Interests: Declaration of competing interest The authors declared no conflicts of interest in connection with the research, authorship, and/or publication of this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen and the major cause of healthcare-associated infections, which are increasingly complicated by the prevalence of highly invasive and hyper-virulent K. pneumoniae strains, necessitating the development of alternative strategies for combatting infections caused by this bacterium. In this study, we successfully constructed a fusion antigen called KP-Ag1, comprising three antigens (GlnH, FimA, and KPN&#95;00466) that were previously identified through reverse vaccinology. Immunization with KP-Ag1 formulated with Al(OH) 3 adjuvant elicited robust humoral and cellular immune response in mice, and conferred protective immunity in a murine model of K. pneumoniae lung infection. Further analysis of serum IgG subtypes from mice immunized with KP-Ag1 revealed a predominant IgG1 response, indicating that KP-Ag1 predominantly induces a Th2-biased immune response. Additionally, opsonophagocytic killing assay suggested that humoral immune responses play a pivotal role in mediating protection conferred by KP-Ag1. Moreover, KP-Ag1 was found to promote the activation and maturation of BMDCs in vitro, which is essential for subsequent efficient antigen presentation. More importantly, vaccination with KP-Ag1 demonstrated cross-protective efficacy against clinical isolates of K. pneumoniae varying in serotypes, antibiotic resistance, and virulence profiles. Therefore, KP-Ag1 holds promise as a candidate for K. pneumoniae vaccine development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: New interventions are available for the prevention of respiratory syncytial virus (RSV) disease in young infants. We aimed to assess the potential impact and cost-effectiveness of using a long-acting monoclonal antibody (RSV mAb) or maternal RSV vaccine in the Argentine context., Methods: We used a static proportionate outcomes model to calculate the costs and consequences of using RSV mAb or maternal RSV vaccine over a ten-year period (2025-2034) in Argentina, assuming both year-round and seasonal administration. We compared each intervention to no pharmaceutical RSV intervention. The primary outcome was the discounted cost per disability-adjusted life year (DALY) averted from a societal perspective. We assumed willingness-to-pay of US$ 12,285 per DALY averted (0.9 times the national gross domestic product per capita). We used population study data on costs and disease burden and the efficacy of clinical trials of both interventions as inputs. We ran deterministic and probabilistic uncertainty analyses., Findings: Either strategy (RSV mAb or maternal RSV vaccine) could prevent >25% of RSV deaths aged <5 years and ∼30% aged <6 months (the age group where most intervention impact occurs). With a dose price of $US 50, both products have a 100% probability of being cost-effective compared to no intervention (US$ 5283 [95%CI $5203-$5363] and US$ 5522 [95%CI $5427 - $5617] per DALY averted for year-round use of RSV mAb and maternal RSV vaccine, respectively). Similar health impact could be achieved by a six-month seasonal strategy, which could improve cost-effectiveness by around 45% (assuming the dose price is unchanged)., Interpretation: Either RSV mAb or maternal RSV vaccine are worth consideration in Argentina when priced at ≤US$ 50 per dose. A seasonal strategy could improve cost-effectiveness., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mauricio Caballero reports financial support was provided by Bill & Melinda Gates Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Infection by SARS-CoV2 has become a challenge, especially for immunocompromised patients who show a weaker humoral response to COVID-19 vaccine. Tixagevimab+cilgavimab (Evusheld) is a combination of human monoclonal antibodies that can be used for pre-exposure prophylaxis to prevent infection or disease by SARS-CoV2., Objectives: Our study aimed to investigate the effectiveness of Evusheld by comparing an Exposed and an Unexposed group., Study Design: Immunocompromised patients were enrolled in the Evusheld Group between March and September 2022. All patients had anti-spike IgG antibody levels <260 BAU/ml before administration of Evusheld. Blood samples for serological evaluations were collected, and anti-Spike antibodies were tested. For the Unexposed Group, a serologic test was performed at enrollment and a questionnaire was performed after 6 months., Results: 43 patients received Evusheld pre-exposure prophylaxis and 45 patients not receiving Evusheld were enrolled in the Unexposed group. The median age was 59.0 years in the Evusheld group, and 63.0 in the unexposed group. In the Evusheld group, during the Omicron wave in Italy, 23.3% of subjects developed symptomatic infection compared to 42.2% in the unexposed group. A majority of infections was seen in male respect to female patients. No difference in length of infection between the groups was seen. Antibody level remained higher than the basal threshold at 180 days from enrollment., Conclusions: Evusheld seems to reduce the rate of symptomatic infection in immunocompromised patients. Further data are required to determine whether this prophylaxis may have a longer-lasting effect over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Vaccinations are important for informal caregivers and their care recipients. Mental health problems are common among care givers. The aim of this study was to investigate vaccination readiness in informal caregivers and associations with mental health issues. Associations between vaccination readiness in informal caregivers and the vaccination status of their aged care recipients were examined., Methods: Within the multicenter prospective registry study 'Bavarian ambulatory Covid-19 Monitor (BaCoM) ', informal caregivers were asked for symptoms of depression (PHQ-9), burden of caretaking (BSFC-s), psychological antecedents of vaccination readiness (5C model) and previous Covid-19 infections of their care recipients. The vaccination status against Covid-19, seasonal influenza and pneumococcal disease was determined via vaccination certificates. Data analysis was performed using ordinal regressions and Mann-Whitney-U tests., Results: Data of n = 91 informal caregivers, associated with n = 84 care recipients were collected. Symptoms of depression were associated with reduced vaccination readiness (Calculation: p = 0.026, OR = 1.18), as well as the perceived burden of caretaking (Confidence: p = 0.006, OR = 0.88). A previous Covid-19 infection of the care recipients was associated with decreased vaccination readiness of informal caregivers (Median (Q1-Q3) Confidence: 5.0 (4.5-6.0) vs. 4.0 (3.0-5.0); Calculation: 5.0 (3.0-6.0) vs. 4.0 (1.0-5.0)). The vaccination status of the care recipients interrelated significantly with vaccination readiness of their informal caregivers (Confidence: p < 0.001; Complacency: p < 0.01; Constraints p < 0.05). No significant interrelations between vaccination readiness and the vaccination status against seasonal influenza or pneumococcal disease occurred., Conclusion: Mental health issues of informal caregivers seem to be associated with the actual vaccination status against Covid-19 in their care recipients. Target group specific counselling as well as an active involvement of informal caregivers in shared decision-making processes can be of relevance, but even more attention should be paid to the protection of mental health for informal caregivers., Trial Registration Number: German Register of Clinical Studies DRKS 26039., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)