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The level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4–5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50 % using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4–5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation. [ABSTRACT FROM AUTHOR]

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]

Health care workers play an essential role in maintaining the public trust in vaccination programmes globally, and more specifically, in low- and middle-income countries. This role is particularly important in building trust in the human papillomavirus (HPV) vaccine. While there are many factors that affect HPV vaccine acceptance, health care workers are one of the most critical influences in the decision-making process among parents as well as adolescent girls. In this paper, we sought to better understand how health care workers in a diverse set of countries communicate and promote HPV vaccines. We summarize communication approaches and lessons learned by health care workers in Kenya, India, and Nigeria through a case study approach. In Kenya, the utilization of a multisectoral approach proved to be very important. In India, intense social mobilization with targeted messaging by target audience laid the groundwork for community acceptance. An evolving communication strategy was essential in Nigeria, where there is no national HPV vaccination programme. Given the increase in vaccine hesitancy globally, the lessons learned through these three country examples highlight the importance of communication efforts in increasing vaccine acceptance. [ABSTRACT FROM AUTHOR]

International stakeholders gathered in New Delhi, India, in December 2022 to share experiences on human papillomaviruses (HPV) prevention and control strategies. As part of a supplementary publication from the meeting proceedings, this paper describes secondary HPV prevention strategies highlighting the varying degrees of progress and challenges through case studies from Bhutan, India, and Türkiye. India has implemented national screening guidelines, primarily using visual inspection with acetic acid (VIA), but achieving a low coverage rate of 1.9% (2022). In contrast, Bhutan and Türkiye have redesigned and established HPV-based cervical screening programs targeting women aged 30–65, achieving 77% (2022) and 95% (2019) coverage among women ever screened, respectively. Lessons learned include utilising patient health information management systems, analysing optimal context-specific HPV testing strategies and ensuring use and continuous supply of clinically validated HPV tests. [ABSTRACT FROM AUTHOR]

This article presents an overview of the main challenges and lessons learned that were presented during the symposia organized by the Coalition to Strengthen the HPV Immunization Community (CHIC) in Africa and South Asia in 2022. Discussions at these meetings revolved around introduction, planning, implementation, and sustainability of HPV prevention and control programmes, with a particular focus in HPV immunisation, as well as cervical cancer screening in South Asian countries. This article also discusses the recently endorsed off-label single-dose HPV vaccination schedule and its potential impact on programme delivery and access. Furthermore, it highlights the importance of intersectional collaboration, effective communication and advocacy strategies, and the need for robust health information systems. Some of the critical factors identified for reducing the burden of cervical cancer in low- and middle-income countries (LMICs) included strategies for increasing access and coverage, addressing vaccine hesitancy, and building capacity among health care providers. The symposia emphasized the importance of face-to-face interactions for collaboration and decision making, with live translation services enabling full participation by stakeholders from diverse backgrounds. The paper concludes with a call for continued collaboration to make progress in reducing the burden of cervical cancer in LMICs. [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]

• There has been a substantial decline in confirmed mumps cases since 2020. • PCR testing decline and IgM testing uptake present reporting challenges. • Only 9 outbreak-associated cases of mumps reported from 2021 to 2023. • 3% of mumps cases were imported, suggesting mumps remains endemic in the US. • Maintaining high MMR coverage is important to prevent future outbreaks. This paper highlights recent clinical complications of mumps reported in the United States and summarizes appropriate confirmatory testing for mumps, encouraging vigilance for mumps disease, an endemic vaccine-preventable illness. Surveillance data from jurisdictions reporting confirmed and probable cases of mumps in the United States were descriptively analyzed to assess epidemiologic trends from January 1, 2018 – December 31, 2023. Data were reported to the National Notifiable Disease Surveillance System and the Epidemiology and Laboratory Capacity Project O. Cases were classified according to the Council of State and Territorial Epidemiologists 2011 mumps case definition. From 2018–2023, United States health departments reported 8,006 confirmed and probable mumps cases to the National Notifiable Disease Surveillance System, of which 85.4% occurred during January 1, 2018–April 4, 2020 and 14.6% during April 5, 2020–December 31, 2023. The incidence of mumps was highest among those aged 18–24 years during 2018–2020 (maximum of 4.54 cases per 100,000 persons in 2019), and highest among those aged 1–4 years during 2021–2023 (maximum 0.67 per 100,000 persons in 2023). Incidence among all age groups during 2021–2023 remained below levels during 2018–2020. Fewer than 12% of mumps cases were confirmed during 2021–2023, compared to >50% during 2018–2019. Although incidence has declined since the COVID-19 pandemic, these surveillance data highlight that mumps remains endemic in the United States. Therefore, maintaining high MMR vaccination coverage is essential to prevent future vaccine-preventable outbreaks and minimize severe complications from infection. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) encourages countries to provide appropriate vaccinations for children, adolescents, and relevant adult populations. Childhood programme have been the focus of global investments, but recent pandemics have increasingly demonstrated the value of life course vaccination. Our objective is to compare national life course immunization programmatic maturity prior to mass COVID-19 vaccine introduction, the largest adult vaccination programme, globally. As coverage estimates (typically used to assess childhood programmes) are not available for adult vaccinations, this analysis pilots a standardized quantitative metric of programmatic maturity. Through consultation with vaccination experts, we developed a standardized approach to assess national immunization programme maturity across the life course. In accordance with expert input, five vaccines were selected to represent delivery across the life course: diphtheria tetanus toxoid and pertussis (DTP); measles (MCV) second dose; human papillomavirus (HPV) final dose; pneumococcal conjugate (PCV) final dose; and seasonal influenza annual dose. Experts recommended inclusion of the following indicators for each vaccine: a legal mandate (national policy), experience delivering the vaccine (programme duration), and vaccine use (uptake for relevant populations). We developed a metric accordingly that provides up to 5 points per vaccine ("vaccine specific maturity score") which when summed forms the "life course maturity score", with a maximum score of 25. We analysed the prevalence of national policies, experience, and use by region and World Bank income group. More than 55% of the 194 WHO Member States had childhood vaccine policies for all three of the vaccines considered (DTP, MCV, and PCV) compared to 60% for HPV (proxy for adolescent vaccination programme) and 52% for seasonal influenza (proxy for adult vaccination programme). Childhood vaccination programmes (e.g., MCV and DTP) had the highest vaccine specific maturity scores, while seasonal influenza and HPV vaccination programmes had much lower scores. The national life course maturity scores ranged from 1 to 23, with a global median of 12 (IQR: 8; 16). The piloted metric provides an overview of the maturity of life course immunization programmes. The metric is structured to be a flexible, rapid resource that can be used to assess other combinations of vaccines across the life course. The findings from this paper provide a baseline of immunization programme maturity for childhood, adolescent, and adult vaccination programmes immediately prior to the COVID-19 vaccine introduction. This maturity score, or adaptations of this approach, could be used to monitor the trajectory of national immunization programme maturity across the life course in the years ahead. [ABSTRACT FROM AUTHOR]

Risk communication tools based on epidemiological models can help inform decision-making, but must be responsive to health literacy needs to be effective. To facilitate informed choice about risks and benefits of COVID-19 vaccination, an epidemiological model called the COVID-19 Risk Calculator (CoRiCal) tool was developed by a multi-disciplinary team. This paper demonstrates how to use health literacy principles to improve consumer understanding of COVID-19 and vaccine effects, using a range of methods that could be applied to any health emergency. Stage 1: Health literacy optimisation and user testing to reduce improve understandability (n = 19). Stage 2: Experiments to explore the effect of risk communication formats on perceived understanding including probability, graphs, evaluative labels and comparison risks (n = 207). Stage 3: Randomised controlled trial (n = 2005) with 4 arms: 1) standard government information; 2) standard CoRiCal output based on bar graphs; 3) animation explaining bar graphs in "x per million" format; 4) animation explaining bar graphs in "1 in x chance" format. The primary outcome was knowledge about COVID-19 risk. Stage 1 reduced the complexity of the text and graphs. Stage 2 showed that different risk communication formats change perceived understanding, with a preference for evaluative labels across 2 experiments and some indication people with lower health literacy had a greater preference for bar graphs. Stage 3 showed both animations increased knowledge compared to standard government information. There was no difference between the probability formats, or by health literacy level. The results showed that simple explanations of complex epidemiological models improve knowledge about COVID-19 and vaccination. This demonstrates how health literacy design principles and short animations can be used to support informed decision making about health emergencies. • People with low health literacy have worse knowledge and health outcomes. • Risk communication tools can simplify complex vaccination evidence. • Health literacy design principles can be used to address consumer needs. • Short animations using multiple risk formats can improve vaccine knowledge. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • We explored parents' childhood vaccine attitudes & experiences in low vaccine uptake London area. • We explored ethnic minority parents' views -whose children are less likely to be vaccinated. • Parents want to speak to trusted, known health professionals about their children's vaccines. • Access barriers influence whether children are vaccinated or vaccinated late in the UK. [ABSTRACT FROM AUTHOR]

In 2016, the World Health Organization recommended that a fractional dose of yellow fever (YF) vaccine could be used in persons 2 years of age or older in response to an emergency that resulted in a global shortage of available YF vaccine. However, this recommendation did not extend to the youngest age group licensed for YF vaccine because there were no published data on the use or safety of fractional dose YF vaccination in children aged 9–23 months. We conducted a single-blind randomized controlled trial, comparing the immunogenicity and safety of fractional one-fifth and one-half doses of Bio-Manguinhos 17DD YF vaccine with full dose in children aged 9–23 months old in Uganda. In this paper, we present the interim analysis on safety. Children aged 9–23 months presenting for routine well-child services were recruited for inclusion at one of three study sites. We collected data during March 26, 2019–August 31, 2020, on all adverse events following immunization (AEFI) during active surveillance for 28 days post-vaccination using multiple collection tools including a diary card with an objective measurement of fever. An independent team from the Uganda national AEFI Committee investigated and classified serious AEFI (SAE) according to Brighton Collaboration Criteria. Among 1053 enrolled children, 672 (64%) were reported to have a non-serious AEFI (NSAE) and 17 (2%) were reported to have a SAE. The most common AEFI were diarrhoea, fever, and rash, each reported by 355 (34%), 338 (33%), and 188 (18%) participants, respectively. Among 17 participants with SAE, eight were reported to have had seizures and five were hospitalised for seizures or other causes (respiratory symptoms, gastrointestinal illness, malaria). Four SAEs (deaths) occurred >28 days after vaccination. There were no reported cases of pre-specified or vaccine-related SAEs. We observed no significant difference in frequency or severity of adverse events among the study groups. Using comprehensive active surveillance monitoring, we did not identify any unexpected safety concerns among children aged <2 years receiving YF vaccination, including with the fractional doses. Although we identified a high number of both serious and non-serious AEFI, none were determined to be causally related to YF vaccination. These results provide evidence for the safety of fractional dose YF vaccination among children aged 9–23 months. • During active surveillance monitoring following yellow fever vaccination, we did not identify any unexpected safety concerns. • We identified a high number of serious and non-serious adverse events, but none were causally related to vaccination. • These results provide evidence for the safety of fractional dose yellow fever vaccination among children aged 9–23 months. [ABSTRACT FROM AUTHOR]

In recent years, India has seen significant improvements in childhood immunization, but rates among the urban poor remain stagnant. Disruptions during COVID-19 pandemic have created further challenges. This paper focuses on how social norms, vaccine confidence, and interpersonal communication independently and jointly affect vaccine intentions among caregivers of infants living in six slum areas in Varanasi, India. Data for this study come from the baseline assessments conducted before implementing the Happy Baby Program, an intervention to improve vaccination attitudes and intentions. In-person interviews (N = 2,058) were conducted with caretakers of children up to two years old. Analyses showed that interpersonal communication about vaccines, descriptive norms, injunctive norms, and vaccine confidence were each associated with intentions to vaccinate in both a bivariate and, except for injunctive norms, a multivariate model. In addition, we found significant interactions among these variables, suggesting that the roles of interpersonal communication and vaccine confidence attenuated the relationship between social norms and vaccination intention. Overall, our model explained 46.2 % of the variance in vaccine intention. Given the strengths of the relationships observed in this study, intervention strategies should focus on enhancing social norms and vaccine confidence to promote vaccination. [ABSTRACT FROM AUTHOR]

• Insect cells can be used to produce viable Virus-like particles (VLPs) based on OaPV3 L1. • VLPs-based ELISA allowed investigating natural immune response to OaPV3 infection. • Anti-VLPs antibodies are useful tools for OaPV3 in situ detection. • OaPV3 VLPs are suitable candidates for the development of prophylactic vaccines. The design of prophylactic and diagnostic tools specific to animal papillomaviruses is hampered by the difficulties of viral in vitro manipulation and by the scarce availability of dedicated biotechnological tools. This paper reports the production of Ovine Papillomavirus 3 (OaPV3)-based virus-like particles (OaPV3-VLPs) in the baculovirus system and their use to investigate host humoral immune response through the establishment of an indirect ELISA test., Polyclonal sera and monoclonal antibodies were generated against OaPV3-VLPs, and their isotype and reactivity were determined. Additionally, antibodies allowed OaPV3 detection in ovine squamous cell carcinoma (SCC) samples by immunohistochemistry. Results encourage the standardization of OaPV3-specific prophylactic and serological diagnostic tools, and open new perspectives for the study of host-viral interaction and SCC development. [ABSTRACT FROM AUTHOR]

• This is the first systematic review to explore cultural and social attitudes towards COVID-19 vaccination and factors associated with vaccine acceptance in adults by identifying and synthesising international evidence. • Study screening and selection were conducted by two independent reviewers to ensure that all relevant studies were included. • Any reviews, commentary/opinion papers, editorials, and grey literature including third sector and government reports and briefings, educational theses, and conference proceedings were excluded. We may have missed important evidence from this. • Meta-analysis was not possible due to the diversity in the characteristics of included studies. To identify and synthesise evidence on cultural and social attitudes towards coronavirus disease 2019 (COVID-19) vaccination and factors associated with vaccine acceptance in the adult population. Systematic review. Six electronic databases were searched (CINAHL, Coronavirus Research Database, Embase, MEDLINE, Nursing and Allied Health Database, and Web of Science Core Collection). Additional studies were identified through Google Scholar and hand searching the reference lists of all studies included in the review. The searches were conducted to identify all relevant studies published in English, from December 2019 to December 2021. The Critical Appraisal Skills Programme (CASP) and Appraisal tool for Cross-Sectional Studies (AXIS tool) were used to critically appraise the quality of included studies. Data were extracted and synthesised narratively. 1260 records were identified, of which 38 studies were included in the review. Low COVID-19 vaccination acceptance rates were found among young people, females, non-medical students, and even some healthcare workers, which were associated with misinformation obtained through social media platforms, unknown side effects, questionable conspiracy theories, and doubts about efficacy and safety. Higher COVID-19 vaccination acceptance rates were due to recommendations from healthcare professionals and government sources, and the perceived increased risk of contracting COVID-19. COVID-19 vaccine acceptance varies across the globe. To increase the acceptance rate of the COVID-19 vaccine, public health education programmes should be promoted effectively and target specifically the groups who are most hesitant to receive the vaccine such as young people, females, and non-medical students. Vaccine hesitancy among healthcare workers can affect vaccination rates as the majority of the population views them as a trustworthy source for vaccine-related knowledge. Staff training is important to enhance their confidence and communication skills in providing information about COVID-19 vaccination to combat the misunderstanding of the public and encourage vaccine uptake. CRD42021248016. [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]

Influenza A matrix protein 2 (M2e) and neuraminidase (NA) antigens are known to play important roles in mounting a broad range of protection. Nonetheless, the protective efficacy of the VLP vaccines co-expressing both M2e and NA antigens has not been explored. In this study, we generated 2020/2021 seasonal influenza H3N1 VLPs that co-expressed either M2e5x (H3N1M2e5x) or N2 (H3N1N2 VLP) antigens. The protective efficacy of these VLPs was assessed by challenge infection with heterologous H3N2 and heterosubtypic H1N1 and H5N1 viruses in mice. Both VLP formulations induced cross-protection against distinct viruses, H3N1M2e5x VLPs elicited higher levels of cross-reactive IgG in sera against H1N1 and H5N1 viruses than H3N1N2 VLPs. Compared to H3N1N2 VLPs, H3N1M2e5x VLPs also induced substantially enhanced germinal center B cell responses while inhibiting IFN-γ production in the lungs. Importantly, H3N1M2e5x VLPs significantly reduced the lung virus titers upon H1N1, H3N2, and H5N1 challenge infections. These results indicated that VLPs comprising the M2e5x antigen are a promising vaccine design strategy that could aid in the pursuit of a universal influenza vaccine., 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.)

The recent entry of multiple vaccines targeting Neisseria gonorrhoeae (Ng) into the clinical development pathway has highlighted the need to establish methods of adequately assessing anti-gonococcal immune responses. Serum bactericidal activity (SBA) is utilized as a measurement of efficacy in licensure of meningococcal vaccines, but the importance of functional antibodies in preventing and/or clearing gonococcal infections remains largely unknown. In an effort to elucidate the utility of SBA as an immune correlate of protection, we sought to develop a standardized high-throughput human complement SBA (hSBA) assay for which any strain of interest could be tested under uniform conditions, with minimal screening of complement required. Utilization of IgG/IgM-depleted pooled human complement serum permitted testing of diverse serum resistant and sensitive gonococcal and unencapsulated meningococcal strains when bacteria were cultured to induce lipooligosaccharide sialylation; only one of nine randomly selected lots demonstrated intrinsic toxicity. The hSBA assay was well suited for use with multiple test serum sources, including rabbit, mouse, and human serum samples, suggesting widespread applicability., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brian Bonk, Chris Lyle and Bob Natuk report a relationship with Pel-Freez Biologicals that includes employment. Brian Bonk reports a relationship with Pel-Freez Biologicals that includes board membership, equity and stock. 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., (Published by Elsevier Ltd.)

Background: A recent conditional recommendation suggests considering live-attenuated vaccines for solid organ transplant recipients, yet the conditions of their safe and effective administration remain unclear., Methods: This prospective study was conducted at Keio University Hospital from 2002 to August 2023. We gave a live-attenuated vaccine to liver transplant (LT) recipients fulfilling criteria for live-attenuated vaccines, including criteria for humoral and cell-mediated immunity. Patient background information, immunization date, vaccine strain, immunosuppressive agents at the time of vaccination, and antibody titers were collected. Factors related to primary and secondary vaccine failure were evaluated to enhance the effectiveness of the live-attenuated vaccine program after LT., Results: Among 67 LT recipients, 54, 55, 47, and 55 received at least one dose of live-attenuated vaccine for measles, rubella, varicella, and mumps, respectively. The difference in vaccine strains, but not the use of two or more immunosuppressive agents, was associated with a lower risk of vaccine failures. Measles vaccine with the AIK-C strain exhibited significantly lower primary and secondary failure rates than the CAM-70 strain (1/38 vs. 4/16, odds ratio: 0.08, 95 % confidence interval [CI]: 0.01-0.80, p = 0.02, and hazard ratio: 0.54, 95 % CI: 0.34-0.85, p = 0.01, respectively). No primary failures were observed with the TO-336 strain of rubella, whereas 4 of 10 LT recipients with the Matsuura strain of rubella did not seroconvert. For mumps, the Hoshino strain showed lower primary failure rates than the Torii strain (15/52 vs. 3/3, p = 0.03)., Conclusion: According to a 20-year long-term study, vaccine strains are the most critical factor influencing primary and secondary vaccine failure in post-transplant live-attenuated vaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masayoshi Shinjoh reports a relationship with Meiji Seika Pharma Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Shionogi and Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with MSD KK that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with FUJIREBIO Inc. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Mitsubishi Tanabe Pharma Corporation that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Taisho 10 Pharmaceutical Co., Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Fujifilm Toyama Chemical Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with The Mainichi Newspapers Co that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Maruho Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Astellas Pharma Inc. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Sumitomo Pharma Co Ltd. that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Daiichi Sankyo Co Ltd. Tokyo Office that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Takeda Pharmaceutical Company Limited that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Japan Vaccine that includes: speaking and lecture fees. Masayoshi Shinjoh reports a relationship with Pfizer Japan Inc. that includes: consulting or advisory. Tetsuo Nakayama reports a relationship with Eiken Chemical Co Ltd. that includes: funding grants. Tetsuo Nakayama reports a relationship with Daiichi Sankyo Inc. that includes: funding grants. Tetsuo Nakayama reports a relationship with Takeda Pharmaceutical Company Limited 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Zika virus (ZIKV) infection is primarily transmitted by mosquitoes and often asymptomatic in most individuals. Infection during pregnancy can lead to severe birth defects such as congenital microcephaly, and currently, there is no approved vaccine for ZIKV. Several studies are investigating the development of ZIKV vaccine using DNA and RNA as well as recombinant protein technologies; however, the outcomes thus far have not been consistently noteworthy. In this study, we designed an mRNA vaccine for ZIKV and evaluated its immunogenicity using a mouse model. Our vaccine, termed 3xEIII, encodes a triple repeat of domain III from the ZIKV E protein. We effectively encapsulated the mRNA within lipid nanoparticles (LNPs), administered 3xEIII to mice via two intramuscular injections, and assessed the induced humoral and cellular immune responses. Specifically, the vaccine elicited neutralizing antibodies that effectively eliminated ZIKV from the organs of challenged mice. Notably, 3xEIII conferred both protective effects and long-term immunity. In subsequent challenges conducted 40 weeks after boosting, immunized mice experienced temporary weight loss but showed significantly reduced viral titers in target organs by the 9th day post-infection. Conclusively from these findings, 3xEIII stands out as a promising noteworthy mRNA vaccine candidate for Zika virus., 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.)

In this study, we developed two plasmid constructs, pJHL270 and pJHL305, for the dual expression of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Gn and Gc glycoproteins in both prokaryotic and eukaryotic systems. The constructs feature a prokaryotic expression controlled by the Ptrc promoter and a eukaryotic expression driven by the cytomegalovirus promoter and Semliki Forest Virus RNA-dependent RNA polymerase. The Gn/Gc antigenic epitope was derived from consensus sequences of 12 SFTSV M segments collected in South Korea and designed for optimal antigen expression. The full antigen was expressed eukaryotically for post-translational modifications, while the epitope construct was expressed prokaryotically. These constructs were electroporated into an attenuated Salmonella Typhimurium strain (JOL2500) for plasmid delivery, resulting in JOL3042 and JOL3045. Successful expression was confirmed via qRT-PCR and western blot analysis. Mice immunized with JOL3042 showed antibody responses as early as two weeks, while JOL3045 elicited responses at six weeks, skewed toward a Th1 response initially, later balancing with Th2. Flow cytometry revealed significant CD3 + CD4 + and CD3 + CD8 + T-cell responses. Both constructs generated neutralizing antibodies, and a challenge study indicated significant reductions in viral loads in the serum, liver, and spleen of vaccinated mice, demonstrating the effectiveness of the Salmonella-mediated delivery system against SFTSV infection. The outcome of the current study may pave the way to develop a safer and more effective Salmonella-mediated vaccine against lethal SFTSV infection in vulnerable populations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John Hwa Lee reports financial support was provided by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1A6A1A03033084 and 2022R1A6A3A01086797). John Hwa Lee reports a relationship with Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education 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: In response to the challenge of maintaining COVID-19 vaccination coverage amidst the pandemic, VillageReach, in collaboration with the Ministry of Public Health Prevention and Hygiene in Kinshasa, DRC, integrated COVID-19 vaccination with routine immunization services at two primary healthcare facilities. This initiative, launched in July 2022, represented the first of its kind in the DRC, aiming to assess the effectiveness and scalability of a multimodal vaccination approach., Methods: Through a rapid appraisal involving key informant interviews and analysis of pre- and post-integration service delivery data, this case study explores the operational dynamics and outcomes of integrating COVID-19 and routine immunizations., Results: Results demonstrated that the integrated approach not only maintained COVID-19 vaccine coverage but also significantly enhanced routine immunization uptake, particularly among under-immunized and zero-dose children. Overall, the vaccination sites, outreach, and integrated health facilities administered 229,983 (33 %) of COVID-19 vaccines in Kinshasa, of which 53 % were referred by community health workers. Additionally, 998 under-immunized children received routine immunizations, of whom 126 were zero-dose children. Key success factors included sustained community health worker engagement, neighborhood-specific strategies, accessible vaccination points, and robust data management. The findings suggest that such integrative strategies can effectively bolster immunization coverage in urban poor communities, offering valuable insights for similar initiatives in the DRC and beyond., Conclusion: This study advocates for sustained investment in innovative immunization models to strengthen primary healthcare systems post-pandemic., 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 no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The SARS-COV2 pandemic caused significant disruptions in immunization delivery. Baseline deficit gaps in immunization completion exacerbated ongoing disparities in immunization coverage in low- and middle-income. Emerging reports focused on global strategies for return to routine immunization schedules. Currently, there are no studies that examined the dual challenge of returning to normal immunization in a conflict-recovery setting, such as the ISIS (Islamic State of Iraq and Syria) occupation of Iraq post-COVID-19 pandemic. The objective of this study was to estimate the number of children in Hadeetha, Iraq from 12 to 24 months of age who continued to be lost to the routine immunization schedule due to the COVID-19 pandemic shutdowns. Random sampling occurred from a compiled district health facility registrar of all children in the target birth cohort who had a 12-month immunization scheduled during the 2020 lockdown and were lost to the immunization schedule. A total of 171 households from the sampling frame were included in the final sample. In this cross-sectional study, survey data was collected on the head of the household, the caregiver and the child. Additional questions assessed vaccine hesitancy, vaccine information trusted sources and COVID-19 impact on healthcare access. A risk factor analysis was applied to assess using Chi-square (Χ 2 ) for predictors of lack of DTP3 (Diphtheria, Tetanus and Polio) third dose completion. Of children in the study, 67.3 % did not complete the 6-antigen series at 12-months of age and 46.2 % were missing DTP3 for vaccines to be completed during the pandemic shutdown. Specific risk factors for lack of immunization for the DTP3 vaccine included area of residence, age and caregiver knowledge of vaccines. Respondents indicated a dependence on mass vaccination campaigns but also indicated a willingness to receive phone reminders and television campaigns about vaccination schedules., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Al-Dahir reports a relationship with Pfizer Inc. that includes: funding grants. Sara Al-Dahir reports a relationship with Genentech Inc. that includes: funding grants. Kawsar Talaat reports a relationship with Pfizer that includes: funding grants. Kawsar Talaat reports a relationship with AstraZeneca Pharmaceuticals LP that includes: funding grants. Kawsar Talaat reports a relationship with Moderna Inc. 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: BBV152 (Covaxin™) is a whole-virion inactivated SARS-CoV-2 vaccine mixed with an immune adjuvant. We aimed to compare immune responses after booster vaccination with heterologous BBV152 versus homologous mRNA vaccine., Methods: We conducted a randomized, participant-blinded, controlled trial. Fifty mRNA-vaccinated participants were enrolled and randomized to receive an mRNA booster (n = 26) or BBV152 (n = 24). Blood samples were collected pre-vaccination, and at Day 7, 28, 180 and 360 post-booster for analysis of humoral and cellular immune responses. Primary end point was the SARS-CoV-2 anti-spike antibody titer at day 28., Results: Recruitment began in January 2022 and was terminated early due to the BBV152 group meeting pre-specified criteria for futility. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBV152 (2004 IU/mL; 95 % confidence interval [CI], 1132-3548) vs mRNA (26,669 IU/mL; 95 % CI, 21,330-33,266; p < 0.0001), but comparable levels of spike-specific CD4 and cytotoxic T-cells were observed. Anti-spike antibody titers remained significantly different at Day 180: BBV152 4467 IU/mL (95 % CI, 1959-10,186) vs mRNA 20,749 IU/mL (95 % CI, 12,303-35,075; p = 0.0017). Levels of surrogate virus neutralizing antibodies against ancestral and Omicron subvariants BA.1 and BA.2 were significantly higher among mRNA recipients at Day 180, including after adjusting for intercurrent infection. By Day 360, anti-spike antibody titers and neutralizing antibody levels against Omicron subvariants became similar between vaccine groups. By the end of the study, 16 in each arm (mRNA 64 % and BBV152 69.6 %) had breakthrough infections and time to COVID-19 infection between vaccine groups were similar (p = 0.63)., Conclusions: Wild-type SARS-CoV-2 anti-spike antibody titer and surrogate virus neutralizing test levels against wild-type SARS-CoV-2 and Omicron subvariants BA.1/BA.2/BA.5 were significantly higher at Day 28 and 180 in individuals who received booster vaccination with an mRNA vaccine compared with BBV152., Clinical Trial Registration Number: NCT05142319., 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: Percentage uptake of some meningococcal vaccines is low in the US. Understanding what drives vaccination preferences may help to increase vaccination rates., Objectives: To determine how attributes of meningococcal vaccines and the availability of a pentavalent (MenABCWY) vaccine profile drive adolescents' and young people's (AYP's) willingness to be vaccinated and parents' and legal guardians' (PLG') willingness for their child to be vaccinated (WTV). To also explore how preferences for meningococcal vaccines vary by participant characteristics., Methods: Vaccine preferences were elicited in a discrete choice experiment (DCE) with AYP aged 16-23 years and PLG of adolescents aged 11-17 years. Participants chose between two hypothetical vaccine profiles that differed in level of protection, dosing, and risks of mild-to-moderate and severe side effects, and a no vaccination profile. Main outcome measures were relative attribute importance (RAI) and WTV. RAI measured the maximum contribution of an attribute to vaccination choice relative to other attributes. WTV compared predicted choice probabilities for the three vaccine profiles., Results: 407 AYP and 394 PLG participated (50.9% male, 78.4% White/Caucasian). Irrespective of vaccine attributes, 59.5% always opted into vaccination and 3.6% always opted out of vaccination. The most important attributes were level of protection (RAI: 33.7%) and risk of mild-to-moderate side effects (RAI: 32.3%). Dosing was more important to PLG (RAI: 5.9%) than AYP (RAI: 2.0%; p < .01). Adding a pentavalent vaccine alternative increased WTV by 3.7 percentage points (PP) for PLG, 2.4 PP for AYP, 16.4 PP for vaccine-hesitant participants, 13.4 PP for participants without health insurance, and 9.6 PP for adults., Conclusion: Level of protection and risk of mild-to-moderate side effects were the most important vaccine attributes. Adding a pentavalent vaccine alternative increased WTV particularly among adults, individuals who were vaccine-hesitant, and individuals without health insurance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katharina Schley reports a relationship with Pfizer Pharma GmbH that includes: employment. Brett Hauber reports a relationship with Pfizer Inc. that includes: employment. Joseph C. Cappelleri reports a relationship with Pfizer Inc. that includes: employment. Paula Peyrani reports a relationship with Pfizer Inc. that includes: employment. Jessica Vespa Presa reports a relationship with Pfizer Inc. that includes: employment. Joshua Coulter reports a relationship with Pfizer Inc. that includes: employment. Chiara Whichello reports a relationship with Evidera Ltd. that includes: employment. Nicolas Krucien reports a relationship with Evidera Ltd. that includes: employment. Sebastian Heidenreich reports a relationship with Evidera Ltd. that includes: employment. The following co-authors are employees of Pfizer and may hold stocks in Pfizer: KS, BH, JC, JCC, PP, and JVP. The following co-authors are employees of Evidera Ltd.: CW, SH, and NK. SH holds minor stocks in Thermo Fisher Scientific as part of his employment with Evidera. 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: To overcome supply issues of COVID-19 vaccines, this partially single blind, multi-centric, vaccine trial aimed to evaluate humoral immunogenicity using lower vaccine doses, intradermal vaccination, and heterologous vaccine schedules. Also, the immunity after a booster vaccination was assessed., Methodology: 566 COVID-19-naïve healthy adults were randomized to 1 of 8 treatment arms consisting of combinations of BNT162b2, mRNA-1273, and ChAdOx1-S. Anti-Receptor-Binding Domain immunoglobulin G (RBD IgG) titers, neutralizing antibody titres, and avidity of the anti-RBD IgGs was assessed up to 1 year after study start., Results: Prolonging the interval between vaccinations from 28 to 84 days and the use of a heterologous BNT162b2 + mRNA-1273 vaccination schedule led to a non-inferior immune response, compared to the reference schedule. A low dose of mRNA-1273 was sufficient to induce non-inferior immunity. Non-inferiority could not be demonstrated for intradermal vaccination. For all adapted vaccination schedules, anti-RBD IgG titres measured after a first booster vaccination were non-inferior to their reference schedule., Conclusion: This study suggests that reference vaccine schedules can be adapted without jeopardizing the development of an adequate immune response. Immunity after a booster vaccination did not depend on the dose or brand of the booster vaccine, which is relevant for future booster campaigns. The trial is registered in the European Union Clinical Trials Register (number 2021-001993-52) and on clinicaltrials.gov (NCT06189040)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Pierre Van Damme reports financial support was provided by Belgian Health Care Knowledge Centre. 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.)

Introduction: Undervaccination and vaccination-related anxieties among marginalised communities like the transgender and gender-diverse (TGD) and disability communities are underexplored in the Indian context. Our study seeks to understand the role of structural and historical inequities in shaping COVID-19 vaccine access for the two communities in India., Methods: Using a participatory qualitative research approach, TGD and disabled individuals were involved in and consulted throughout the research process. We interviewed 45 individuals for our study, hailing from the two communities and other key stakeholders and health system representatives involved in vaccination roll-out in India. We conducted an inductive thematic analysis guided by the socio-ecological model and intersectionality approach., Results: Despite intent to get vaccinated among most participants, several structural barriers shaped COVID-19 vaccine access for people from the TGD and disability community. This included information and communication gaps with respect to the specific health needs of the two communities, barriers related to vaccine registration, data collection, transport, infrastructure and actual or anticipated mistreatment at vaccine centres. Each emergent structural gap in vaccination had parallels in past health systems experiences, pointing to the longstanding and pervasive inequities within health and allied systems which impact how communities perceive and respond to new health system interventions., Conclusion: This study uncovers the structural inequities within health systems that have permeated the planning, design and outreach of COVID-19 vaccination programs in India. Moving beyond notions of vaccine hesitancy among the TGD and disability community, we underscore the importance of socio-historical contexts of marginalisation and advocate for systems to recognise these contexts and respond equitably to the vaccination and health needs of the two communities. While some challenges among the two communities were distinct, the study explores how a shared experience of exclusion from public systems can provide avenues for cross-movement advocacy and solidarity, and help inform health system reforms., 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: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya., Methods: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung., Results: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes., Conclusion: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch., 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.)

Pneumococcal conjugate vaccines (PCV) typically consist of capsular polysaccharides from different S. pneumoniae serotypes which are covalently attached to carrier protein. A well-established process to manufacture PCV is through activating polysaccharide by oxidation of vicinal diols to aldehydes, followed by protein conjugation via reductive amination. Polysaccharide activation is a crucial step that affects vaccine product critical attributes including conjugate size and structure. Therefore, it is highly desired to have robust analytical methods to well characterize this activation process. In this study, using pneumococcal serotype 6A as the model, we present two complimentary analytical methods for characterization of activated polysaccharide. First, a size exclusion chromatography (SEC) method was developed for quantitative measurement of polysaccharide activation levels. This SEC method demonstrated good assay characteristics on accuracy, precision and linearity. Second, a gold nanoparticle labeled cryo-electron microscopy (Cryo-EM) technique was developed to visualize activation site distribution along polysaccharide chain and provide information on activation heterogeneity. These two complimentary methods can be utilized to control polysaccharide activation process and ensure consistent delivery of conjugate vaccine products., 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.)

In response to the pervasive challenges posed by online health misinformation, our objective was to develop a training program aimed at enhancing the skills and confidence of healthcare workers in recognizing and effectively responding to misinformation, with a particular focus on vaccinations. This article discusses the design of a training program aimed at equipping healthcare workers with the skills to combat health misinformation, offering theoretical foundations for integrating evidence-based strategies into problem-based learning to help learners retain and apply information, and also shares examples and insights gained from its application across diverse learner groups. The training curriculum integrates evidence-based misinformation intervention strategies, learner engagement strategies and draws from authentic scenarios across diverse cultural contexts. The trainings were administered from January through July 2023 to 287 participants across eight countries (Cameroon, Guyana, India, Kenya, Mozambique, Nigeria, Philippines, and the United States) in English, French, Spanish, and Portuguese. Throughout the implementation of the training, a key emphasis was placed on a learner-driven approach that fostered real-world application. Participants engaged in role-playing exercises and problem-solving sessions, enabling them to practice their newfound skills in a controlled setting. Our findings contribute to the literature of participatory, problem-based learning for healthcare professionals and vaccine communication and misinformation response, and can serve as a resource for practitioners implementing similar trainings., 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.)

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains one of the top three causes of death. Currently, the only licensed vaccine against TB is the bacillus Calmette-Guerin (BCG), which lacks efficacy in preventing and controlling pulmonary TB in adults. We aimed to evaluate a nasal TB vaccine formulation composed of the Mtb-specific vaccine antigen ESAT-6, an Mtb-associated protein that can trigger protective immune responses, and S100A4, a recently characterized novel mucosal adjuvant. Mice were intranasally given recombinant ESAT-6 in the presence or absence of S100A4 as an adjuvant. We have provided experimental evidence demonstrating that S100A4 admixed to ESAT-6 could induce Mtb-specific adaptive immune responses after intranasal immunization. S100A4 remarkably augmented the levels of anti-ESAT-6 IgG in serum and IgA in mucosal sites, including lung exudates, bronchoalveolar lavage fluid (BALF) and nasal lavage. Furthermore, in both lung and spleen tissues, S100A4 strongly promoted ESAT-6-specific expansion of CD4 T cells. Both CD4 and CD8 T cells from these tissues expressed increased levels of IFN-γ, TNF-α, and IL-17, cytokines critical for antimicrobial activity. Antigen-reencounter-induced T cell proliferative responses, a key vaccine performance indicator, were augmented in the spleen of S100A4-adjuvanted mice. Furthermore, CD8 T cells from the spleen and lung tissues of these mice expressed higher levels of granzyme B upon antigen re-stimulation. S100A4-adjuvanted immunization may predict good mucosal protection against TB., 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.)

Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who had experienced possible allergic symptoms after their first intramuscular dose of a COVID-19 mRNA vaccine with a 1/5th fractional intradermal test dose of the mRNA-1273 (Moderna) COVID-19 vaccine. No anaphylactic reactions were observed after intradermal vaccination (n = 56). Serum anti-S1 IgG concentrations were measured using a bead-based multiplex assay four weeks after vaccinations. Antibody concentrations were compared with a previously collected nationwide cohort that had received two intramuscular doses of mRNA-1273. Antibody responses in all subjects tested (n = 47) were comparable to standard of care intramuscular dosing. Fractional intradermal dosing of mRNA COVID-19 vaccines may provide a pragmatic solution that is safe, time efficient compared to skin prick testing, dose sparing and immunogenic in individuals with suspected vaccine allergy., 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: Parents are the primary decision makers for their children's vaccination, yet, we have limited knowledge on what influences their decision making related to COVID-19 vaccination. The study aimed to understand these different considerations that shape the decisions of parents of children aged 5-11 years old., Methods: We conducted a qualitative study that included online focus group discussions (FGDs) with parents of children aged 5-11 years old. Data was collected between July 26th, 2022, and February 15th, 2023. A total of eight FGDs were conducted, audio-recorded and transcribed verbatim. Thematic analysis was conducted, and peer debriefing was used to ensure methodological rigor., Results: Findings revealed that parents of vaccinated and unvaccinated children employed language of risk-benefit analysis to inform their decision-making. Parents of vaccinated children highlighted concerns about spreading COVID-19, family member's health, and long COVID-19. For parents of unvaccinated children, they perceived potential vaccine side effects as more harmful than the risks associated with COVID-19. Participants contended that there was a lack of transparency from the government and public health agencies, highlighting inconsistent messaging which had fractured their trust in COVID-19-related recommendations and mandates., Conclusions: Our results indicate that improved transparency on how evidence is developed and why recommendations and mandates shift during the pandemic would foster trust in the government and public health agencies. Open communication with health providers on the potential risks and benefits would also improve caregivers confidence in the vaccine., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shaun Morris reports financial support was provided by Public Health Agency of Canada. Pierre-Philippe Piche-Renaud reports a relationship with Pfizer that includes: funding grants. Shaun K. Morris reports a relationship with Pfizer that includes: board membership. Shaun K. Morris reports a relationship with GlaxoSmithKline Inc. that includes: speaking and lecture fees. Shaun K. Morris reports a relationship with Sanofi Pasteur Inc. that includes: board membership. Shaun K. Morris reports a relationship with Apotex that includes: board membership. 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. Conflicts of interest PPPR has previously been a co-investigator on an investigator-led project funded by Pfizer that is unrelated to the present study. SKM has received honoraria for lectures from GlaxoSmithKline and has been a member of ad hoc advisory boards for Pfizer, Sanofi Pasteur, and Apotex, all unrelated to this study. All other authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil., Methods: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays., Results: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination., Conclusions: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation., 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 no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Several studies described that COVID-19 vaccinations can cause menstrual disorders. Our study aimed to describe whether this also resulted in more general practitioner (GP) consultations for menstrual disorders after COVID-19 vaccination, based on a large cohort study., Methods: A retrospective self-controlled cohort study was performed including vaccinated women in 2021 aged 12-49 years from two large, representative GP databases in the Netherlands. Incidence rates and incidence rate ratio's (IRR) were calculated using Poisson regression, adjusting for SARS-CoV-2 infection as time-varying confounder. The exposed period was set at maximum six months after each COVID-19 vaccination and the non-exposed period was defined as all-time outside the exposed period., Results: The cohort included 631,802 women, of which 18,986 (3 %) consulted the GP for a menstrual disorder during 2021. Increased GP consultations were observed among 12-14 year olds for amenorrhea/hypomenorrhea/oligomenorrhea (IRR: 1.85, 95 % CI: 1.30-2.65) and irregular/frequent menstruation (IRR: 1.33, 95 % CI: 1.06-1.69) after COVID-19 vaccination in general, and after Pfizer/BioNTech vaccination (IRR: 1.87, 95 % CI: 1.31-2.67 for amenorrhea/hypomenorrhea/oligomenorrhea and IRR: 1.35, 95 % CI: 1.06-1.70 for irregular/frequent menstruation). Persons from this age group were in general also vaccinated with Pfizer/BioNTech. No increase in the frequency of GP consultations were observed for older age groups, other vaccine brands, and potential risk groups., Conclusion: For the majority of women, no increased GP consultations for menstrual disorders was found. Solely for the youngest age group (12-14 year olds) increased GP consultations for specific types of menstrual disorders was found after Pfizer/BioNTech vaccination., 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.)