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Following the 1892 cholera pandemic, Richard Pfeiffer, Director of the science section of Robert Koch's Institute for Hygiene in Berlin, began laboratory-based studies on the pathogenesis of the disease using an animal model. These investigations resulted in his discovery of bacterial endotoxin; recognition of the bacteriolytic properties of both animal and human immune sera; and identification of the specific nature of protective immune responses. His research led naturally from cholera to typhoid fever and in November 1896 Pfeiffer published the results of experimental studies on a typhoid vaccine. In September 1896 Almroth Wright, a professor of pathology in the British Army Medical School, published a short note entitled "Typhoid Vaccination". It was appended to a review on the use of styptics to control defective blood coagulation: his previous research studies had a physiological basis that stemmed from earlier studies on tissue fibrinogen. In December 1895, Wright had been commissioned by the Army Medical Department to develop a typhoid vaccine and he later admitted that such work began only after he had spoken with Pfeiffer. In January 1897 Wright published a further paper in which he claimed precedence over Pfeiffer in the introduction of anti-typhoid vaccination. This self-entitlement has subsequently been accepted, primarily because the British Army approved typhoid vaccination in 1914 at the beginning of the First World War. That time has been used as their starting point by many of Wright's biographers, but without any attempt to confirm Wright's claim to priority. This paper concludes Richard Pfeiffer, not Almroth Wright, provided the first account of human typhoid vaccination. It also provides early examples of laboratory-based responses to pandemic and epidemic infectious diseases. [ABSTRACT FROM AUTHOR]

• One and two doses of rubella containing vaccines (RCV) are highly immunogenic for a long period of time. • RCV are effective in preventing rubella and CRS. • RCV are safe. Rubella containing vaccines (RCV) prevent rubella virus infection and subsequent congenital rubella syndrome (CRS). To update the evidence on immunogenicity, duration of protection, effectiveness and safety of RCV, we conducted a systematic literature review. We searched EMBASE and SCOPUS, using keywords for rubella vaccine in combination with immunogenicity (seroconversion and seropositivity), duration of protection, efficacy/effectiveness, and safety. Original research papers involving at least one dose of RCV (at any age), published between 1-1-2010 and 17-5-2019 were included. Where appropriate, meta-analyses were performed. Quality of included studies was assessed using GRADE methodology. We included 36 papers (32 randomized controlled trials (RCTs) and 4 observational studies) on immunogenicity (RA27/3 strain) in children and adolescent girls, 14 papers (5 RCTs and 9 observational studies) on duration of protection, one paper on vaccine effectiveness (VE) (BRDII strain), and 74 studies on safety, including three on safety in pregnancy. Meta-analysis of immunogenicity data showed 99% seroconversion (95% CI: 98–99%) after a single dose of RCV in children, independent of co-administration with other vaccines. Seroconversion after RCV1 below 9 months of age (BRDII strain, at 8 months) was 93% (95% CI: 92–95%). For duration of protection, the included studies showed a seropositivity of 88%-100% measured 1–20 years after one or two RCV doses. The single study on VE of BRDII strain, reported 100% VE after one and two doses. Among 34,332 individuals participating in the RCTs, 140 severe adverse events (SAEs) were reported as possibly related to RCV. Among the case reports on SAEs, the association with RCV was confirmed in one report (on fulminant encephalitis). Among 3,000 pregnant women who were inadvertently vaccinated, no SAEs were reported. One and two doses of RCV are highly immunogenic for a long period of time, effective in preventing rubella and CRS, and safe. [ABSTRACT FROM AUTHOR]

• The mass campaign carried out by the emergency import of OPV in 1961 achieved great results for polio control in Japan. • School influenza vaccination in the 1960–80 s was discontinued without adequate and proper evaluation. • The judgment by the Tokyo High Court in 1992 and the discontinuation of the use of the MMR vaccine in 1993 were attributed for the creation of the so-called 'vaccine gap.' • In the revision of the Immunization Act in 1994, a big change was added to individual vaccination by 'obligation to make efforts.' • From around 2010, efforts have been made to bridge 'vaccine gap' and establish the global standard in vaccination. This paper reviews the administration related to vaccination in Japan after the enactment of the Immunization Act in 1948, under which vaccination was implemented mandatory for the public. To enhance the effectiveness of vaccination activities, the government implemented group vaccination, which is convenient for vaccinating recipients all at once. In 1976, Japan established the relief system for health damage after vaccination. While some projects, such as the mass administration of live oral polio vaccine in 1961, achieved excellent results, incidents leading to health damage occurred, such as the diphtheria toxoid immunization incident (1948) and frequent occurrence of aseptic meningitis owing to the measles, mumps, and rubella vaccine (1989). In December 1992, the Tokyo High Court sentenced that the onset of health damage after vaccination could be attributed to the negligence of the national government. In the revision of the Immunization Act in 1994, the "mandatory vaccination" enforced until then was changed to "recommended vaccination." The Act was also changed to recommend "individual vaccination" in principle, which is performed after primary care physicians investigate the physical condition of individual recipients and carefully conduct preliminary examination. For approximately 20 years from the 1990s, a vaccine gap existed between Japan and other countries. From around 2010, efforts have been made to bridge this gap and establish the global standard in vaccination. [ABSTRACT FROM AUTHOR]

• Introduction of the vaccine coincided with a reduced number of RVGE hospitalisations in public hospitals in Ireland amongst children under 5 years. While this effect was lagged (1 year), the impact is sustained. • Post vaccine, RVGE hospitalised patients were more likely to be older than 2 years with a lower length of stay on average. • Potential cost savings for the Irish healthcare system; the average annual reduction in hospitalisations (n = 492) with an estimated economic value of €0.92 million annually. Rotavirus gastroenteritis (RVGE), a vaccine preventable disease, remains a common cause of severe gastroenteritis in children globally. Ireland introduced the universal rotavirus vaccination to the national immunisation programme in 2016. In this paper the economic impact on RVGE related hospitalisations amongst children under 5 years is examined. Using national data from all Irish public hospitals, an Interrupted Times Series Analysis (ITSA) compares RVGE hospitalisations amongst children under 5 years, pre- and post-vaccine introduction. Costs are estimated and ITSA results are compared to the counterfactual to estimate the economic impact of the vaccine. A probit model examines patient characteristics pre- and post-vaccine introduction. Vaccine introduction coincided with lowered RVGE related hospitalisations. While this effect was delayed (1 year) there is evidence of a sustained impact. RVGE patients' post-vaccine introduction were likely to be over 2 years (p = 0.001) and length of stay was lower on average (p = 0.095). The counterfactual analysis revealed 492 RVGE hospitalisations were avoided on average annually since the introduction of the vaccine. This has an estimated economic value of €0.92 million per annum. Following the introduction of the rotavirus vaccine in Ireland, hospitalisations for RVGE decreased significantly and those hospitalised were older and with a reduced length of stay on average. This has the potential for significant cost savings for the Irish healthcare system. [ABSTRACT FROM AUTHOR]

The polio endgame strategy calls for ending the use of and removal of all Sabin vaccines globally given the risks of generation and spread of cVDPVs. With the successful eradication of wild poliovirus type 2 in 2015, the process of removing type 2 Sabin vaccines began with the switch from tOPV to bOPV across national vaccination programs. Following the tOPV to bOPV switch in April/May 2016, monovalent type 2 OPV (mOPV2) has been put into use in response to detected cVDPV2 polioviruses outbreaks. Between 31 May 2016 and 30 Jun 2020, 453 million doses of mOPV2 were provided to 21 countries to conduct 235 campaigns to respond to cVDPV2 outbreaks and high-risk events. However, the use of this vaccine paradoxically reintroduces live attenuated type 2 poliovirus into the populations and the environment, therefore, poses a risk for the emergence of new VDPV2s. Thus, it is critical to carefully and appropriately manage all in-country mOPV2 stocks utilized in outbreak response to minimize this risk. In this article, we examine the performance of mOPV2 vaccine management utilized for various outbreak responses after the switch. We present the major challenges faced and the lessons learned, to improve technical guidance and future response activities. Performance varied significantly across countries in terms of each of the activity areas evaluated. There were major gaps, especially in terms of vaccine accountability, and in many instances large numbers of vials went unaccounted presenting additional risk for further VDPV2 emergences. We have shown that especially at the beginning of implementation, insufficient attention has been given to mOPV2 vaccine management. Enhanced focus on mOPV2 vaccine management in line with the lessons learned presented in this paper should be a priority for public health programs and countries to consider and adapt in future VDPV2 responses as well as potential future activities associated with eventual complete withdrawal & cessation of OPV. These experiences can also be extended to other vaccines for which strict stock management and containment measures are required. [ABSTRACT FROM AUTHOR]

• Community pharmacies continued to serve as immunization sites during the pandemic. • Types of vaccines administered in 2020 and 2019 were similar. • 95% of pharmacies continued to offer vaccines to walk-in patients in 2020. • 48% of pharmacies made vaccines available through appointments in 2020. • 50% of pharmacies offered vaccines outside the pharmacy (e.g.: curbside) in 2020. Immunization rates for seasonal and non-seasonal vaccines dropped during the COVID-19 pandemic. Little is known about the extent to which community pharmacies in the USA continued to serve as immunization sites during the pandemic. This study compared 1) the types and perceived changes in non-COVID-19 vaccine doses administered at rural community pharmacies in 2020 (during the pandemic) to 2019 (pre-pandemic) and 2) the delivery of non-COVID-19 immunization services in 2020 to 2019. A mixed-mode (paper/electronic) survey of a convenience sample of 385 community pharmacies operating in rural settings and have administered ≥1 vaccine in 2019 and 2020 was distributed in May-August 2021. Survey development was informed by relevant literature, pre-tested with three individuals, and pilot-tested with 20 pharmacists. Non-response bias was assessed, and survey responses were analyzed using descriptive and bivariate statistics. Of the 385 community pharmacies, 86 qualified pharmacies completed the survey (Response Rate = 23.8%). The percentage of pharmacies offering a given vaccine in 2019 and 2020 were similar; with one exception, a higher percentage of pharmacies reported having MMR administered for adults in the pharmacy in 2020 (McNemar's test; p-value = 0.0253). For each given vaccine, the majority of respondents did not perceive a change in the number of doses administered in 2020 compared to 2019. Further, the majority reported no difference in how they delivered immunization services during and pre-pandemic. However, a small percentage of respondents (6.0–22.0%) adapted their services by adopting several measures to ensure the safety and continuity of immunizations during the pandemic. Findings highlight the importance of community pharmacies as immunization sites during the pandemic. Community pharmacies continued immunization delivery at community pharmacies during the pandemic with almost no noticeable change to types and doses of vaccines compared to pre-pandemic nor the process of vaccine delivery. [ABSTRACT FROM AUTHOR]

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings. [ABSTRACT FROM AUTHOR]

Vaccination is the most celebrated and denigrated achievement of medicine and public health – not only today, but since Edward Jenner's time (1798). In fact, the idea of injecting a mild form of "disease" into a healthy person was attacked even earlier than the discovery of vaccines. The forerunner of Jenner's vaccination with bovine lymph was the inoculation of smallpox material from person to person, which, known in Europe since the beginning of the eighteenth century, was a target of harsh criticism. The reasons for criticizing the Jennerian vaccination and its mandatory practice were medical, anthropological, biological (vaccination is not safe), religious and ethical (it is wrong to inoculate a healthy person with disease), and political (vaccination is a threat to individual freedom). As such, anti-vaccination groups emerged in England, where inoculation was adopted early, as well as overall in Europe and in the United States. This paper focuses on the lesser known debate that arose in Germany in the years 1852–53 about the medical practice of vaccination. This is an a important topic of public health that has aroused a wide debate and comparison especially in recent years and now with pandemic on Sars-Cov-2 (Covid-19) and will probably be the subject of further reflection and consideration in the coming years. [ABSTRACT FROM AUTHOR]

In the development of new vaccines, many trials use age de-escalation : after establishing safety and efficacy in adult populations, progressively younger cohorts are enrolled and studied. Age de-escalation promotes many values. The responsibility to protect children from potential risks of experimental vaccines is significant, not only given increased risks of adverse effects but also because parents and medical professionals have a moral responsibility to protect children from harms associated with novel, uncertain interventions. Further, given that young children cannot provide informed consent, acceptable risks for research requiring proxy consent are lower than for adults making decisions for themselves. Although age de-escalation approaches are widely used in vaccine trials, including notably in the recent development of pediatric COVID-19 vaccines, ethicists have not addressed the benefits and risks of these approaches. Their benefits are largely assumed and unstated, while their potential risks are usually overlooked. There are no official ethics guidelines for the use of age de-escalation in clinical research. In this paper, we provide a systematic account of key moral factors to consider when employing age de-escalation. Analyzing pediatric COVID-19 vaccine development as our key case study, we clarify the benefits, risks, and trade-offs involved in age de-escalation approaches and call for the development of evidence-based best practice guidelines to identify when age de-escalation is likely to be an ethical strategy in vaccine development. [ABSTRACT FROM AUTHOR]

• Europe needs a sustainable system for timely, high-quality evidence on vaccine benefits and risks. • European vaccine stakeholders have different perspectives but similar information needs. • The ADVANCE project (now VAC4EU) has developed and tested a system to generate the necessary evidence. The influenza A/H1N1 pandemic in 2009 taught us that the monitoring of vaccine benefits and risks in Europe had potential for improvement if different public and private stakeholders would collaborate better (public health institutes (PHIs), regulatory authorities, research institutes, vaccine manufacturers). The Innovative Medicines Initiative (IMI) subsequently issued a competitive call to establish a public-private partnership to build and test a novel system for monitoring vaccine benefits and risks in Europe. The ADVANCE project (Accelerated Development of Vaccine benefit-risk Collaboration in Europe) was created as a result. The objective of this paper is to describe the perspectives of key stakeholder groups of the ADVANCE consortium for vaccine benefit-risk monitoring and their views on how to build a European system addressing the needs and challenges of such monitoring. These perspectives and needs were assessed at the start of the ADVANCE project by the European Medicines Agency together with representatives of the main stakeholders in the field of vaccines within and outside the ADVANCE consortium (i.e. research institutes, public health institutes, medicines regulatory authorities, vaccine manufacturers, patient associations). Although all stakeholder representatives stated they conduct vaccine benefit-risk monitoring according to their own remit, needs and obligations, they are faced with similar challenges and needs for improved collaboration. A robust, rapid system yielding high-quality information on the benefits and risks of vaccines would therefore support their decision making. ADVANCE has developed such a system and has tested its performance in a series of proof of concept (POC) studies. The system, how it was used and the results from the POC studies are described in the papers in this supplementary issue. [ABSTRACT FROM AUTHOR]

In 2016, the Sierra Leone Ministry of Health and Sanitation (MoHS) piloted VaxTrac, an electronic immunization registry (EIR), in an urban district to improve management of vaccination records and tracking of children who missed scheduled doses. We aimed to document lessons learned to inform decision-making on VaxTrac and similar EIRs' future use. Ten out of 50 urban health facilities that implemented VaxTrac were purposively selected for inclusion in a rapid mixed-method assessment from November to December 2017. For a one-month period, records of six scheduled vaccine doses among children < 2 years old in VaxTrac were abstracted and compared to three paper-based records (register of under-two children, daily tally sheet, and monthly summary form). We used the under-two register as the reference gold standard for comparison purposes. We interviewed and observed 10 heath workers, one from each selected facility, who were using VaxTrac. Overall, VaxTrac captured < 65% of the vaccine doses reported in the paper-based sources, but in the largest health facility VaxTrac captured the highest number of doses. Two additional notable patterns emerged: 1) the aggregated data sources reported higher doses administered compared to the under-two register and VaxTrac; 2) data sources that need real-time data capture during the vaccination session reported fewer doses administered compared to the monthly HF2 summary form. Health workers expressed that the EIR helped them to shorten the time to manage, summarize, and report vaccination records. Workflows for data entry in VaxTrac were inconsistent among facilities and rarely integrated into existing processes. Data sharing restrictions contributed to duplicate records. Although VaxTrac helped to shorten the time to manage, summarize, and report vaccination records, data sharing restrictions coupled with inconsistent and inefficient workflows were major implementation challenges. Readiness-to-introduce and sustainability should be carefully considered before implementing an EIR. [ABSTRACT FROM AUTHOR]

• Enhanced Safety Surveillance for seasonal influenza vaccines is mandatory in EU since 2014/15. • Data from Enhanced Passive Safety Surveillance for Influvac® and Influvac® Tetra are presented. • Passive surveillance implemented for Influvac® & Influvac® Tetra complies with EU requirements. • Results confirm the favourable safety profiles of Influvac® and Influvac® Tetra. In 2014, the European Medicines Agency (EMA) set out requirements for an enhanced safety surveillance for seasonal influenza vaccines. This paper presents data from the yearly Enhanced Passive Safety Surveillance (EPSS) implemented for Influvac® since season 2014/15 and continued for Influvac® Tetra from season 2018/19 onwards. In seven consecutive seasons, an EPSS, aiming for at least 1,000 vaccinees (additional target of 100 vaccinees per five predefined age groups), was conducted in Germany, where market characteristics were expected to allow for a quick generation of representative data. Reactogenicity data in terms of reporting rates, severity and duration of pre-specified local and systemic adverse events of interest (AEI) were collected using response cards, which were completed by vaccinees and returned seven days after vaccination via regular mail. In addition, response cards contained a call center number to enhance reporting of other than pre-specified adverse events. The primary target of at least 1,000 vaccinees was surpassed in all seasons, as was the additional target of 100 adults and elderly. Reactogenicity data were in line with known safety profile of Influvac® and Influvac® Tetra. In children, the target was mostly met in seasons when the EPSS was conducted for Influvac®, but not in seasons when it was conducted for Influvac® Tetra. Although the data for Influvac® Tetra are based on a low number of paediatric vaccinees, they do not indicate a different reactogenicity profile of Influvac® Tetra compared with Influvac®. No signals were identified. The EPSS set up for Influvac® and Influvac® Tetra proved a robust and effective methodology to comply with the objectives of EMÁ's guidance on enhanced safety surveillance of seasonal influenza vaccines. Safety data from seven consecutive seasons confirmed the favourable safety profile of both vaccines. [ABSTRACT FROM AUTHOR]

• Almost two-thirds of Ghanaian high school students have some intention, and one quarter have strong intentions to participate in HPV vaccination. • Higher vaccination intention scores were associated with stronger beliefs about vaccine effectiveness and free vaccination programmes, and recommendations from social networks (i.e., parents, religious leaders) and healthcare providers. • Perceived barriers to HPV vaccination were associated with lower vaccination intention scores. Cervical cancer is the second most common cancer and the second leading cause of cancer death among women in Ghana. HPV vaccination is expected to be added to the national vaccination schedule in 2023. This study aimed to: i) describe intentions to participate in HPV vaccination and ii) explore factors associated with vaccination intentions among female senior high school students in Ghana. Female students (aged 16–24) were recruited from 17 senior high schools in Ashanti Region. A cross-sectional anonymous self-report paper-and-pen survey assessed students' HPV vaccination intentions using three items, and a range of correlates (individual, parent/family, social networks, service provision). Descriptive statistics were calculated for vaccination intentions, and correlates of intention scores (where higher scores indicate stronger intentions) were explored with a linear mixed-effect model. Of 2400 participants, 64% (95%CI: 62%, 67%) agreed with at least one vaccination intention item. Uncertainty and disagreement with at least one item were endorsed by 51% (95%CI: 49%, 53%) and 44% (95%CI: 42%, 46%) of students, respectively. One-quarter of the students (25%, 95%CI: 23%, 26%) agreed, 12% (95% 11%, 13%) disagreed, and 11% (95%CI: 10%,13%) indicated uncertainty, on all three vaccination intention items. Vaccination uptake was 4.5%. Students were likely to have higher vaccination intention scores if: they had stronger beliefs about vaccine effectiveness; vaccination was recommended by parents, religious leaders and service providers, and vaccinated peers; and it was free. Students were likely to have lower vaccination intention scores if they perceived barriers to vaccination (e.g., side effects). While two-thirds of students had some intention to participate in HPV vaccination, vaccine hesitancy (i.e., uncertainty or disagreement) was apparent. Alongside the rollout of a free national vaccination programme, messaging about vaccination benefits and effectiveness targeting students, as well as parents, religious leaders, service providers and peers would be beneficial given their influential role in students' vaccination intentions. [ABSTRACT FROM AUTHOR]

Pediatric immunization is important for preventing potentially life-threatening diseases in children. Over time, the number of recommended pediatric vaccines has increased and is likely to increase further as new vaccines are developed. Given the different number of doses for available vaccines and various constraints (e.g., the appropriate age for each dose of a vaccine or the time between doses), it is challenging to develop a recommended vaccination schedule or a catch-up schedule when a child falls behind on one or more vaccinations. We developed an integer programming optimization model, enabled by Python programming and embedded into an Excel-based decision tool, to recommend childhood vaccination schedules or personalized catch-up schedules. The model recommends a vaccination schedule that balances the goal of being as close as possible to the clinically-indicated dosing schedules and the goal of minimizing clinic visits, and gives users the ability to trade off between these two goals. We illustrated the broad applicability of our proposed model with commonly-faced vaccine scheduling challenges in the United States. The illustrative computational case study confirms our model's ability to create personalized schedules based on each child's age and vaccination history, and to adjust appropriately when a new vaccine becomes available. The model presented in this paper fills the need for an easy-to-use tool to recommend vaccination schedules for de novo and catch-up purposes. It provides straightforward recommendations that can be easily used by physicians, is flexible to handle the requirements varying by region, and can be updated as new vaccines are approved for use. [ABSTRACT FROM AUTHOR]

• This paper provides an overview of the key trends and themes of discussion concerning attitudes to and the adoption of two health measures to control COVID-19 in the UK and US. • Using social media data collected via Twitter, we explore how different public groups react when confronted with mandatory policies. • We find two constituencies have been brought together: pre-existing vaccine critical 'anti-vaccine' groups and newly formed oppositional COVID-19 groups. • The oppositional COVID-19 constituencies vary in composition and nature, but the central focus is a disagreement about the seriousness and threat of COVID-19 and public health measures to control COVID-19. What unites many disparate interests is an aversion to mandates. Protests starting in the summer of 2020, notedly in the US and UK, have brought together two constituencies: pre-existing anti-vaccine groups and newly formed oppositional COVID-19 groups. The oppositional COVID-19 groups vary in composition and nature, but the central focus is a disagreement about the seriousness and threat of COVID-19 and with the public health measures to control COVID-19. What unites many disparate interests is an aversion to mandates. The compulsion to undertake particular public health activities such as mask-wearing and vaccination is a complex topic of public attitudes and beliefs alongside public health goals and messaging. We aim to analyse social media discussions about facemask wearing and the adoption of potential vaccines for COVID-19. Using media monitoring software MeltwaterTM, we analyse English-language tweets for one year from 1st June 2020 until 1st June 2021. We pay particular attention to connections in conversations between key topics of concern regarding masks and vaccines across social media networks. We track where ideas and activist behaviours towards both health interventions have originated, have similarities, and how they have changed over time. Our aim is to provide an overview of the key trends and themes of discussion concerning attitudes to and adoption of health measures in the control of COVID-19 and how publics react when confronted with mandatory policies. We draw on an already extensive literature about mandatory vaccination policies to inform our assessment, from psychology and behavioural science to ethics, political theory, sociology, and public policy. [ABSTRACT FROM AUTHOR]

The development of several types of vaccines to avert COVID-19 has taken place. Despite several reports of undesirable reactions noted post-COVID-19 vaccine administration, later remains one of the best prevention and management tools in fighting the spread of the virus and its variants and reducing the harshness of this viral attack. The purpose of the current paper was to explore the side‐effects experienced by the females in the Eastern Province of Saudi Arabia directly after receiving the booster dose of the Pfizer-BioNTech/BNT162b2 COVID‐19 vaccine. A descriptive cross-sectional study among adults living in the East-ern Province, Saudi Arabia was applied. A survey link was, distributed through WhatsApp, SMS, or e-mail to community members. Respondent's demographic information was acquired, as well as information about any local and systemic side‐effects reported following booster dose of BioNTech/BNT162b2 COVID‐19 vaccine. A total of 72.36% (432/597) of the respondents who participated in this study reported at least one side‐effect. Pain and redness at the injection site (75.93%), myalgia (71.99%), headache (53.24%), fever (33.56%), and fatigue (43.78%) were the highest frequently stated side‐effects. Furthermore, 9.25% of the respondents had to see a physician due to side effects, plus merely four participants were admitted to the hospital. The respondents working in the non-healthcare-related sector had a 1.677‐fold more possibility of side effects in comparison with the other respondents (adjusted odds ratio = 1.677; 95% CI = 1.363, 2.064). All reported side‐effects were mild to moderate. These findings might persuade pessimists and refusers to get the COVID-19 vaccine. Myalgia and pain or redness at the site of injection were the most common reported side-effects in our study. [ABSTRACT FROM AUTHOR]

COVID-19 vaccine hesitancy is currently-one of the main obstacles to worldwide herd immunity and socioeconomic recovery. Because vaccine coverage can vary between and within countries, it is important to identify sources of variation so that policies can be tailored to different population groups. In this paper, we analyze the results from a survey designed and implemented in order to identify early adopters and laggers in six big cities located in Argentina, Colombia, Chile, Ecuador, Peru, and Dominican Republic. We find that trust in government and science, accurate knowledge about the value of vaccination and vaccine effects, and perceived risk of getting sick is associated with a higher probability to get vaccinated. We also identify potential laggers such as women and populations with high education but low knowledge about vaccines. We discuss specific strategies to promote vaccination among these populations groups as well as more general strategies designed to gain trust. These findings are specific to the context of Latin America insofar as the underlying factors associated with the choice to be vaccinated vary significantly by location and in relation to individual-level factors. [ABSTRACT FROM AUTHOR]

This paper considers the problem of patient scheduling and capacity planning for the vaccination process during the COVID-19 pandemic. The proposed solution is based on a non-linear mathematical modeling approach representing the dynamics of an open Jackson Network and a Generalized Network. To test these models, we proposed three objective functions and analyzed different configurations of the process corresponding to various levels of the models' parameters as well as the conditions present in the case study. To assess the computational performance of the models, we also experimented with larger instances in terms of number of steps or stations used and number of patients scheduled. The computational results show how parameters such as the minimum percentage of patients served, the maximum occupation allowed per station and the objective functions used have an impact on the configuration of the process. The proposed approach can support the decision-making process in vaccination centers to efficiently assign human and material resources to maximize the number of patients vaccinated while ensuring reasonable waiting times, number of patients in queue and servers' utilization rates, which in turn are key to avoid overcrowding and other negative conditions in the system that could increase the risk of infections. [ABSTRACT FROM AUTHOR]

Despite vaccination being one of the most effective public health interventions, there are persisting inequalities and inequities in immunisation. Understanding the differences in subnational vaccine impact can help improve delivery mechanisms and policy. We analyse subnational vaccination coverage of measles first-dose (MCV1) and estimate patterns of inequalities in impact, represented as deaths averted, across 45 countries in Africa. We also evaluate how much this impact would improve under more equitable vaccination coverage scenarios. Using coverage data for MCV1 from 2000–2019, we estimate the number of deaths averted at the first administrative level. We use the ratio of deaths averted per vaccination from two mathematical models to extrapolate the impact at a subnational level. Next, we calculate inequality for each country, measuring the spread of deaths averted across its regions, accounting for differences in population. Finally, using three more equitable vaccination coverage scenarios, we evaluate how much impact of MCV1 immunisation could improve by (1) assuming all regions in a country have at least national coverage, (2) assuming all regions have the observed maximum coverage; and (3) assuming all regions have at least 80% coverage. Our results show that progress in coverage and reducing inequality has slowed in the last decade in many African countries. Under the three scenarios, a significant number of additional deaths in children could be prevented each year; for example, under the observed maximum coverage scenario, global MCV1 coverage would improve from 76% to 90%, resulting in a further 363(95%CrI:299–482) deaths averted per 100,000 live births. This paper illustrates that estimates of the impact of MCV1 immunisation at a national level can mask subnational heterogeneity. We further show that a considerable number of deaths could be prevented by maximising equitable access in countries with high inequality when increasing the global coverage of MCV1 vaccination. [ABSTRACT FROM AUTHOR]

Abstract: During the pandemic (H1N1) 2009 vaccination campaign, vaccine providers collected immunization data using hybrid (paper-based and electronic methods) and electronic data systems. We measured staff time in seconds spent on data collection tasks to compare system efficiencies. The sample consisted of 38 organizations across nine Canadian provinces/territories. The total mean data collection times per client were 104s (electronic system), 143s (hybrid system with electronic registration) and 172s (hybrid system with paper registration). Electronic registration and record keeping were faster than paper-based methods; these findings should be used to improve data collection for future influenza seasons. [Copyright &y& Elsevier]

• Vaccination of badgers may reduce the spread of bovine tuberculosis to cattle. • The paper examines evidence of risk compensation and spillover behaviours amongst farmers. • Increased risk taking by farmers is associated with vaccination. • Risk compensation is linked to low self-efficacy amongst farmers. • Lack of spillover behaviour is due to low cultural saliency of vaccination. This paper analyses farmers' behavioural responses to Government attempts to reduce the risk of disease transmission from badgers to cattle through badger vaccination. Evidence for two opposing behavioural adaptions is examined in response to the vaccination of badgers to reduce the risk of transmission to farmed cattle. Risk compensation theory suggests that interventions that reduce risk, such as vaccination, are counterbalanced by negative behavioural adaptions. By contrast, the spillover effect suggests that interventions can prompt further positive behaviours. The paper uses data from a longitudinal mixed methods study of farmers' attitudes to badger vaccination to prevent the spread of bovine tuberculosis, their reports of biosecurity practices, and cattle movement data in 5 areas of England, one of which experienced badger vaccination. Analysis finds limited evidence of spillover behaviours following vaccination. Lack of spillover is attributed to farmers' beliefs in the effectiveness of biosecurity and the lack of similarity between badger vaccination and vaccination for other animal diseases. Risk compensation behaviours are associated with farmers' beliefs as to who should manage animal disease. Rather than farmers' belief in vaccine effectiveness, it is more likely that farmers' low sense of being able to do anything to prevent disease influences their apparent risk compensation behaviours. These findings address the gap in the literature relating to farmers' behavioural adaptions to vaccine use in the management of animal disease. [ABSTRACT FROM AUTHOR]

• Digital supply chain information system linked to immunization registry, serves 6M. • Digital system includes stock notifications, dashboards and peer networks. • Overall stockout rate significantly lower with digital system vs. legacy system. • More time with digital system increases odds of vaccine availability. Since 2016, the Government of Tanzania has been implementing TImR, an integrated Electronic Immunization registry-logistics management information system (EIR-LMIS) that includes stock notifications. The objective of this study is to estimate the impact of this intervention on vaccine availability. Monthly stock-out data were collected from paper registers at facilities, an Excel-based system at districts, and the new system (TImR) across all 924 health facilities in Arusha, Tanga and Kilimanjaro Regions. Six months of stockout rates pre- and post-introduction, by antigen, were compared via a two-way analysis of variance (ANOVA). A mixed-effects logistic regression model with the TImR data identified predictors of vaccine availability across antigens. Post-introduction, ANOVA models estimated that overall stock-out rates declined from a monthly average of 7.1% to 2.1% (p < 0.01). Three specific vaccines had fewer stock-outs; OPV's monthly average dropped from 12.5% to 2.1% (p < 0.01), MR from 9.4% to 1.0% (p < 0.01) and DTP-HepB-HiB from 8.1% to 1.7% (p < 0.01). In the mixed-effects logistic regression model, controlling for antigen, odds of stock-out were 4.1% (95% CI: 3.3 – 4.9) lower for each week of tenure. Compared to DTP-HepB-HiB vaccine, odds of BCG vaccine being stocked out were 4.31 as high (95% CI: 3.1 – 5.0). The odds of being stocked-out were 29.7% lower for PCV (95% CI: 8.8 – 45.8) and 26.6% (95% CI: 3.4 – 44.1) lower for rotavirus vaccines compared to DTP-HepB-HiB. The odds of stock out were 37.7% lower for MR vaccine than DTP-HepB-HiB (95% CI: 18.1 – 52.6). Tanzania's integrated EIR-eLMIS may increase vaccine availability compared to its paper and Excel based system. Post-introduction of an eLMIS, the odds of a vaccine stock-out reduced over time. Further research could determine the impact of this intervention on vaccine wastage and replenishment response times. [ABSTRACT FROM AUTHOR]

Recombinant viral vaccines expressing antigens of pathogenic microbes (e.g., HIV, Ebola virus, and malaria) have been designed to overcome the insufficient immune responses induced by the conventional vaccines. Our knowledge of and clinical experience with the new recombinant viral vaccines are insufficient, and a clear regulatory pathway is needed for the further development and evaluation of recombinant viral vaccines. In 2018, the research group supported by the Ministry of Health, Labour and Welfare, Japan (MHLW) published a concept paper to address the development of recombinant viral vaccines against infectious diseases. Herein we summarize the concept paper—which explains the Japanese regulatory concerns about recombinant viral vaccines—and provide a focus of discussion about the development of recombinant viral vaccines. [ABSTRACT FROM AUTHOR]

Abstract: Measles control remains a great challenge in Uganda. We conducted a prospective study among household contacts aged 9–59 months to assess measles vaccination effectiveness. Index cases were measles patients seen in Kampala hospitals in 1999. Measles was diagnosed in 37/43 (86%) of unvaccinated and in 33/145 (23%) of vaccinated exposed contacts, respectively. Vaccination effectiveness was 74% (95% CI; 64–81), which was lower than expected. This may indicate the need for strengthening of the cold chain and/or introduction of a second opportunity for measles vaccination, either as part of the routine immunization program or in the form of supplementary immunization activities. [Copyright &y& Elsevier]

• Ormutivimab is the third recombinant human anti-rabies monoclonal antibody marketed in the world. In China, it is the first. • The study reported in this paper is the first phase IIb clinical study carried out in China. It further evaluates the activity, safety and immunogenicity of Ormutivimab combined with rabies vaccine, and recommends a reasonable dosage for phase III confirmatory clinical study. • In this study, the activity and safety of Ormutivimab combined with rabies vaccine were compared with that of commercial HRIG combined with vaccine and vaccinated alone. • In this study, the effects of different doses of Ormutivimab on active immunization of rabies vaccine were evaluated and compared with that of commercially available HRIG. • This study evaluated the dose correlation of Ormutivimab immunogenicity (anti-antibody) and the effect of anti-antibody on the activity. This study was a randomized, double-blind, parallel-controlled trail to evaluate the rabies virus neutralizing activity（RVNA）, safety and immunogenicity of Ormutivimab + rabies vaccine in Chinese healthy adults. Subjects were randomly and equally assigned to 4 groups (20 IU/kg Omtv + vaccine, 40 IU/kg Omtv + vaccine, 20 IU/kg HRIG + vaccine, and placebo + vaccine). Subjects received vaccine as the WHO Essen regime combined with Omutivimab、HRIG or placebo on Day 0. The study lasted for 43 days. A total of 240 subjects were simultaneously assigned to both FAS and SS. Fifty subjects with baseline RVNA > 0.05 IU/ml (detection limit) were excluded, 190 were included into mITT. All the subjects from 40 IU/kg Omtv + vaccine group had a protection level of RNVA (≥0.5 IU/ml, WHO) on Day 14, and those in 20 IU/kg Omtv + vaccine group and placebo + vaccine group converted positive 100 % on Day 28. In contrast to 20 IU/kg HRIG + vaccine and placebo + vaccine, Ormutivimab + vaccine provided a higher RVNA during Days 0 to 7. And RVNA in 40 IU/kg Omtv + vaccine and 20 IU/kg Omtv + vaccine groups were always higher than 20 IU/kg HRIG + vaccine group during the whole study. Although anti-Omtv antibody were detected in some subjects, it did not influence the RVNA. The incidence of adverse reactions was significantly lower in 20 IU/kg Omtv + vaccine group (17.2 %) than in 40 IU/kg Omtv + vaccine (36.7 %) and 20 IU/kg HRIG + vaccine groups (40.3 %). Compared with HRIG + vaccine and placebo + vaccine, Omtv + vaccine provided higher RNVA for earlier immune protection. The interference of Ormutivimab on the long-term immune protection induced by rabies vaccine is weaker than HRIG. At the same dose, the adverse reactions of Omtv + vaccine group were less than HRIG + vaccine group. Registration: ClinicalTrials.gov #NCT02559921. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness. [ABSTRACT FROM AUTHOR]

There is little research to understand reasons for suboptimal influenza vaccination uptake among Aboriginal people of different ages in Australia. This study aimed to better understand the communication needs and preferences of Aboriginal families (Phase 2) in New South Wales, Australia, and their health service providers (Phase 1), to inform future interventions to improve influenza immunisation coverage in Aboriginal communities. This paper reports from Phase 1 of the study. Aboriginal and non-Aboriginal researchers designed and conducted the study, with cultural governance provided by Aboriginal health care professionals and other community members working within health departments or community healthcare settings across Australia. In Phase 1 we conducted interviews and focus groups with 18 Aboriginal immunisation providers and mainstream immunisation co-ordinators from three geographic areas in New South Wales. We used group-based thematic analysis with a cultural lens and sought participants' feedback prior to finalising results. We identified four themes, framed as opportunities for improvement: better supporting Aboriginal Medical Services as providers of influenza vaccinations; improving the accessibility and appropriateness of mainstream services for Aboriginal families; improving health providers' knowledge of Aboriginal people' influenza risk and their willingness to recommend vaccination; and engaging communities to design influenza vaccination resources. To achieve optimal influenza vaccination coverage, all health services must take responsibility for providing culturally responsive clinical care to Aboriginal families. We suggest that, where possible, mainstream services incorporate elements of the family-centred and broader model of health used by Aboriginal Medical Services. This includes creating a welcoming environment, appropriately identifying and getting to know Aboriginal patients, taking a preventative approach, and opportunistically offering and strongly encouraging influenza vaccination to the individual and their family. [ABSTRACT FROM AUTHOR]

• Russia demonstrates low vaccination intentions compared to most European countries and some emerging economies. • The paper uses a nationally representative dataset for Russia (RLMS HSE-2020) to analyze the scope of COVID-19 vaccination hesitancy and resistance prior to the start of the vaccination campaign. • 43% of the Russian adult population were resistant towards vaccination, while 13% were hesitant. • Vaccination attitudes depend on age, family composition, education, type of settlement, employment, self-rated health, previous COVID-19 experience, and self-perceived risk of being infected. • Personality traits, risk attitudes, and trust, reflect the deep-rooted causes of vaccination attitudes and strongly predict vaccination intentions. Vaccination is the main tool available to handle the COVID-19 pandemic globally. Though no vaccine is proven to be 100% effective, vaccination secures against getting seriously ill and dying from the disease. Russia announced the development of its first domestic vaccine back in August 2020 and launched the nationwide immunization campaign at the beginning of 2021. Despite these achievements, as of mid-October 2021, only 36% of the population got at least one shot of the vaccine. Massive vaccination hesitancy and refusal pose a great threat to public health and postpone social and economic recovery. Using nationally representative data from the general adult population of Russia, this study explores the scope of vaccination hesitancy and refusal as well as the determinants of vaccination attitudes. The results suggest that only 45% of the Russian population demonstrated positive attitudes towards the COVID-19 vaccination prior to the launch of a nationwide vaccination program. We analyze a wide array of demographic, socio-economic, and health-related factors in relation to vaccination intentions and explore the deep-rooted causes of vaccination reluctance by looking at personality traits, religiosity, and trust. The obtained results are vital for designing policy measures to promote vaccination. [ABSTRACT FROM AUTHOR]

• A total of 33 advanced vaccinology courses were in existence in 2021. • Some vaccinology courses were not sustained since 2018. • The number of vaccinology courses has been increasing during the last few years, with courses offered in each WHO region. • The COVID-19 pandemic resulted in the cancellation or postponement of some vaccinology courses. • Due to the COVID-19 pandemic, an increased number of courses are using an online or hybrid format. The rapid development of innovations and new technologies, the focus on the life-course approach to immunization and equity, and the prevalent hesitancy towards vaccines requires immunization staff to be well-trained and updated regularly in order to deliver quality immunization services to the public. The need for advanced vaccinology training is therefore paramount. In preparation for a second Global Workshop on Advanced Vaccinology Training that took place in March 2022, this paper presents the results of a survey aiming to provide a thorough update of a landscape analysis on advanced vaccinology courses conducted in 2018 and a look at the impact of the COVID-19 crisis. Thirty-three course organizers responded to a survey to provide information on their respective course. Of those, 17 courses are short courses, 11 post-graduate courses and 5 are Master level courses. Most courses are organized on an annual basis. Even though some courses were not sustained overtime, the number of courses has been increasing during the last few years, and at least one vaccinology course is now being offered in each WHO region. Although the training capacity has increased tremendously, the need still exceeds the capacity and many courses have way more applicants than they can select. The most frequent challenges reported included sustainable funding and identifying faculty. The COVID-19 pandemic impacted the delivery of several vaccinology courses, which have been postponed or reformatted to an online or hybrid training event. An e-portal of the global collaboration has been established to facilitate communication between the different courses and to assist future course participants to identify the most suitable course for their needs. [ABSTRACT FROM AUTHOR]

• There are major cross-provincial differences in child vaccination coverage in PNG. • Travel time to health facilities lowers vaccination coverage among children in PNG. • Travel time to health facilities disproportionately affects vaccination among poor. • Cross-provincial coverage differences exist even after accounting for travel time. With infant and child mortality rates that are among the highest in the Pacific region, and basic vaccination coverage rates that are 39% among children 12–23 months, increased coverage of vaccines is a high priority investment for Papua New Guinea (PNG). Using recently gathered household survey data for PNG, this paper contributes to the evidence-base for enhancing investments in frontline facilities by examining the implications of travel time to health facilities for basic vaccination coverage among children in PNG. We find that vaccination coverage rates among children 12–23 months old in PNG are decreasing in distance to healthcare facilities; and this holds whether the outcome is receipt of basic vaccinations (BCG; 3 dose pentavalent; OPV3; Measles), or basic vaccinations-plus (basic vaccinations + Hepatitis B + PCV3). We also find that travel time to health facilities lowers vaccination rates among children 12–23 months old in poor households to a greater extent than for children from richer households. Thus, enhanced geographical access to and resourcing of frontline facilities is likely to expand not only immunization coverage, lower mortality and increase aggregate economic gains, but also improve the distribution of immunization coverage in PNG across socioeconomic groups. [ABSTRACT FROM AUTHOR]

• Comprehensive review of recent literature on zero- or missed-dose children in Nigeria. • Risk factors are well-known and widely studied. • Literature on interventions was scattered, and focussed on campaigns and polio. • Gaps exist in investigating how to deliver sustainable immunization programs. • Further work is needed to operationalise findings of this review. 'Zero-dose' refers to a person who does not receive a single dose of any vaccine in the routine national immunization schedule, while 'missed dose' refers to a person who does not complete the schedule. These people remain vulnerable to vaccine-preventable diseases, and are often already disadvantaged due to poverty, conflict, and lack of access to basic health services. Globally, more 22.7 million children are estimated to be zero- or missed-dose, of which an estimated 3.1 million (∼14 %) reside in Nigeria. We conducted a scoping review to synthesize recent literature on risk factors and interventions for zero- and missed-dose children in Nigeria. Our search identified 127 papers, including research into risk factors only (n = 66); interventions only (n = 34); both risk factors and interventions (n = 18); and publications that made recommendations only (n = 9). The most frequently reported factors influencing childhood vaccine uptake were maternal factors (n = 77), particularly maternal education (n = 22) and access to ante- and perinatal care (n = 19); heterogeneity between different types of communities – including location, region, wealth, religion, population composition, and other challenges (n = 50); access to vaccination, i.e., proximity of facilities with vaccines and vaccinators (n = 37); and awareness about immunization – including safety, efficacy, importance, and schedules (n = 18). Literature assessing implementation of interventions was more scattered, and heavily skewed towards vaccination campaigns and polio eradication efforts. Major evidence gaps exist in how to deliver effective and sustainable routine childhood immunization. Overall, further work is needed to operationalise the learnings from these studies, e.g. through applying findings to Nigeria's next review of vaccination plans, and using this summary as a basis for further investigation and specific recommendations on effective interventions. [ABSTRACT FROM AUTHOR]

Numerous countries and jurisdictions have implemented differential COVID-19 public health restrictions based on individual vaccination status to mitigate the public health risks posed by unvaccinated individuals. Although it is scientifically and ethically justifiable to introduce such vaccination-based differentiated measures as a risk-based approach to resume high-risk activities in an ongoing pandemic, their justification is weakened by lack of clarity on their intended goals and the specific risks or potential harms they intend to mitigate. Furthermore, the criteria for the removal of differentiated measures may not be clear, which raises the possibility of shifting goalposts without clear justification and with potential for unfairly discriminatory consequences. This paper seeks to clarify the ethical justification of COVID-19 vaccination-based differentiated measures based on a public health risk-based approach, with focus on their deployment in domestic settings. We argue that such measures should be consistent with the principal goal of COVID-19 vaccination programmes, which is to reduce the incidence of severely ill patients and associated healthcare burdens so as to protect a health system. We provide some considerations for the removal of vaccination-based differentiated measures based on this goal. [ABSTRACT FROM AUTHOR]

• Patients were extremely satisfied with COVID-19 vaccination in pharmacies. • Accessibility, proximity and short waiting times were some of the reasons. • Patients' motivation for vaccination was primarily to protect themselves from severe COVID-19. • Pharmacists stated difficulties to provide this service due to personnel shortage. • Physicians rather appreciated the relief on their workload. COVID-19 vaccinations applied in pharmacies can facilitate accessibility and potentially increase the vaccination rate but remain controversial in many countries. This study aimed to explore the patients' motivation to receive their COVID-19 vaccination in a pharmacy and examine patient and provider satisfaction with this novel service. The study was designed as an explorative cross-sectional multicenter in-house quantitative survey and was conducted during the first weeks of COVID-19 vaccinations in German pharmacies from February to April 2022. The survey consisted of a paper-based questionnaire with scaling questions, multiple choice questions and open questions. Patients were recruited consecutively before their vaccination and completed the survey directly after the service. Vaccinating pharmacists were also invited to answer a questionnaire on their experiences, motivation and expectations. A total of 427 questionnaires out of 11 pharmacies were be included. The overall patient satisfaction with vaccinations in pharmacies was rated with the highest remarks by 91.5% of the participants, another 7.8% were fairly satisfied. Patient satisfaction with scheduling, waiting time, information, hygiene, vaccination technique and a feeling of safety was very high (96.5–97.9%). Patients' motivation on COVID-19 vaccination was to prevent severe COVID-19 symptoms (88.9%) and to protect others (72.3%). Easy accessibility, low barriers and proximity were other reasons for utilizing this service, mentioned by 61.8% of the patients. Pharmacists were highly motivated and found the task meaningful but experienced considerable personnel shortage. General practitioners rather expressed relief on their workload. Data of this study strongly supports to include pharmacies as additional providers of COVID-19 vaccinations. Patients stated marked satisfaction with this setting and expressed a feeling of safety and trust. Whereas most patients may have utilized the service for convenience, easy accessibility and low barriers were appreciated and can potentially contribute to higher vaccination rates. [ABSTRACT FROM AUTHOR]

While African countries have improved access to immunization since the start of the millennium, progress has stagnated in the last few years. One in five African children is not vaccinated with life-saving vaccines, and recent outbreaks of vaccine-preventable diseases (VPDs) including yellow fever, measles, and meningitis, among others point to gaps in immunization coverage as well as disease surveillance. In 2017, African Heads of State endorsed the Addis Declaration on Immunization (ADI) at the 28th African Union Summit and committed to ensuring universal access to immunization across the continent. Since then, countries have taken several steps to translate the ADI commitments into tangible progress. However, the continent continues to face challenges in delivering immunization services, including limited vaccine-related funding, inequitable access to immunization services and weak surveillance systems. In the absence of concerted political will, COVID-19 threatens to reverse progress made so far. This paper reflects on the effects of political will in shaping the immunization agenda on the continent and the continued need for political commitment to deliver on the ADI commitments in a post-COVID world. Data were gathered from the regular national immunization reports, WHO/UNICEF estimates of immunization coverage as well as case studies of country implementation on ADI. [ABSTRACT FROM AUTHOR]

Inactivated viral vaccines have long been used in humans for diseases of global health threat (e.g., poliomyelitis and pandemic and seasonal influenza) and the technology of inactivation has more recently been used for emerging diseases such as West Nile, Chikungunya, Ross River, SARS and especially for COVID-19. The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit and risk of several vaccine platform technologies, including inactivated viral vaccines. This paper uses the BRAVATO inactivated virus vaccine template to review the features of an inactivated whole chikungunya virus (CHIKV) vaccine that has been evaluated in several preclinical studies and clinical trials. The inactivated whole CHIKV vaccine was cultured on Vero cells and inactivated by ß-propiolactone. This provides an effective, flexible system for high-yield manufacturing. The inactivated whole CHIKV vaccine has favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the current inactivated whole CHIKV vaccine safety database with unblinded data from the ongoing studies: 850 participants from phase II study (parts A and B) outside of India, and 600 participants from ongoing phase II study in India, and completed phase I clinical studies for 60 subjects. Overall, the inactivated whole CHIKV vaccine has been well tolerated, with no significant safety issues identified. Evaluation of the inactivated whole CHIKV vaccine is continuing, with 1410 participants vaccinated as of 20 April 2022. Extensive evaluation of immunogenicity in humans shows strong, durable humoral immune responses. [ABSTRACT FROM AUTHOR]

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit-risk assessment of several vaccine platform technologies, including nucleic acid (RNA and DNA) vaccines. This paper uses the BRAVATO template to review the features of a vaccine employing a proprietary mRNA vaccine platform to develop Moderna COVID-19 Vaccine (mRNA-1273); a highly effective vaccine to prevent coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In response to the pandemic the first in human studies began in March 2020 and the pivotal, placebo-controlled phase 3 efficacy study in over 30,000 adults began in July 2020. Based on demonstration of efficacy and safety at the time of interim analysis in November 2020 and at the time of trial unblinding in March 2021, the mRNA-1273 received Emergency Use Authorization in December 2020 and full FDA approval in January 2022. [ABSTRACT FROM AUTHOR]

[Display omitted] • Al oxyhydroxide and Al hydroxyphosphate have different physico-chemical properties: a key role on the biological effects. • The charges of Al oxyhydroxide and Al hydroxyphosphate are not modified by the antigen in vaccines except in the case of Infanrix Hexa®. • The mixing between Al oxyhydroxide and Al hydroxyphosphate does not occur at the elementary particle level in vaccine. • The dilution of vaccines or adjuvants leads to a decrease of the size of particles, which can have an impact on the induced cellular mechanisms. Aluminum salts have been used as adjuvants in human vaccines since 1932. The most used adjuvants are Al oxyhydroxide (AlOOH) and Al hydroxyphosphate (AlOHPO 4). Al adjuvants have different physico-chemical properties. The differences in these properties are not well documented and not considered by the Food and Drug Administration (FDA), though they can largely influence biological effects of the adjuvants which are particulate components. In this study, different physico-chemical properties including the shape, size and charge of particles have been evaluated under different conditions in three Al adjuvants containing-vaccines and two corresponding commercial adjuvants suspensions. The results showed that the two Al adjuvants have different shapes, sizes and charges but both form aggregates. In addition, a clear effect of dilution on the size of the aggregates was observed. Moreover, different sizes of Al particles were measured for both Al oxyhydroxide adjuvant alone or in the vaccine, at identical concentrations, displaying the impact of adsorbed proteins on the size of aggregates in the case of the vaccine. Taken together, this paper suggests the importance to evaluate, before any biological and especially toxicological impact study, the whole physico-chemical properties of Al particle without restricting to the sole evaluation of the injected concentration. Furthermore, any modification of these mentioned parameters during manipulation, before animal or cell exposure, should be considered. In a more global way, the fixed "safe dose" of Al adjuvants should be specific for each type of Al adjuvant independently or for a mix of the two compounds, due to their different properties. [ABSTRACT FROM AUTHOR]

[Display omitted] • Economic evaluation (EE) considers few of 18 vaccination value concepts identified. • Expert analysis identified 3 priority concepts to expand EE of vaccines. • Selection criteria included decision-making relevance and measurement feasibility. • Priorities: macroeconomic impact, social ethics/equity, health system strengthening. • Relevant robust methods and evidence are needed to support new value elements in EE. A value of vaccination framework for economic evaluation (EE) identified unique value concepts for the broad benefits vaccination provides to individuals, society, healthcare systems and national economies. The objectives of this paper were to work with experts in developed countries to objectively identify three priority concepts to extend current EE. The previously developed classification of value concepts in vaccination distinguished 18 concepts, categorised as conventional payer and societal perspective concepts and novel broader societal concepts. Their inclusion in current EE guidelines was assessed. Experts identified eight criteria relevant to decision-making and measurement feasibility, which were weighted and used to score each concept. The relative ranking of concepts by importance and the gaps in guidelines were used to identify three priority concepts on which to focus immediate efforts to extend EE. The EE guidelines review highlighted differences across countries and between guidelines and practice. Conventional payer perspective concepts (e.g., individual and societal health gains and medical costs) were generally included, while gaps were evident for conventional societal perspective concepts (e.g., family/caregiver health and economic gains). Few novel broader societal benefits were considered, and only in ad hoc cases. The top-three concepts for near-term consideration: macroeconomic gains (e.g., benefiting the economy, tourism), social equity and ethics (e.g., equal distribution of health outcomes, reduced health/financial equity gaps) and health systems strengthening, resilience and security (e.g., efficiency gains, reduced disruption, increased capacity). Gaps, inconsistencies and limited assessment of vaccination value in EE can lead to differences in policy and vaccination access. The three priority concepts identified provide a feasible approach for capturing VoV more broadly in the near-term. Robust methods for measuring and valuing these concepts in future assessments will help strengthen the evidence used to inform decisions, improving access to vaccines that are demonstrably good value for money from society's point of view. [ABSTRACT FROM AUTHOR]

Childhood Immunization is one of the critical strategies to decrease infant morbidity and mortality due to infectious diseases, but primary immunization schedules for infants in most countries start at 2 months of age. Childhood vaccines therefore begin providing adequate protection later in life, leaving infants vulnerable to infectious diseases and creating an immunity gap that results in higher morbidity and mortality among younger infants. Maternal immunization, the practice of vaccinating individuals during pregnancy, reduces the risk of infant infection primarily through the transfer of protective maternal antibodies to the fetus during late pregnancy. Although much progress has been made in public health policies to support maternal immunization research, inclusion of pregnant individuals and children in clinical trials remains challenging. This has resulted in paucity of evidence regarding safety and effectiveness of vaccines to support licensure of products intended for use during pregnancy and lactation to prevent disease in the infant. In addition, although safeguards for clinical research in pregnancy are supportive, experimental vaccines, e.g., Respiratory Syncytial Viru s, are more complicated to study because data on safety, efficacy, and dosing are limited. This requires randomized controlled trials with safety monitoring for the mother, the fetus, and the infant with follow-up for at least 1 year or longer to assess long-term health outcomes that may be associated with peripartum vaccine exposure. The goal of this paper is to discuss the general regulatory considerations for clinical research to evaluate safety and effectiveness of vaccines administered during pregnancy to protect infants from disease. This could be useful to inform future vaccine trials. This discussion is not intended to provide agency guidance nor to articulate agency policy. [ABSTRACT FROM AUTHOR]

Vaccines have produced remarkable impact in reducing the global burden of disease. Thanks to Gavi-the Vaccine Alliance, which supports eligible countries to increase access to the new and underused vaccines. Gavi support depends on economic growth, whereby low-income countries contribute 0.2 USD per dose of supported vaccines, while middle-income countries contribute by price fraction that increases gradually by 15% annually. A country must become fully self-financing within five years when its economy reaches 1,630 USD GNI per capita. Recently, Tanzania, Benin, Haiti, Nepal, and Tajikistan became middle-income countries triggering gradual reduction in Gavi support. This paper first compares the socio-demographic characteristics, immunization program performance, and health financing strategies of these countries and second, explores domestic financing strategies that Tanzania can use to close the funding gap. Although the five countries are similar economically, they vary in demography, health financing strategies, extent of donor dependency, and strength of immunization programs. Some health indicators are not any better than those in low-income countries. Tanzania receives the largest financial support from Gavi and is projected to be fully self-financing by 2043. The potential domestic funding opportunities include to increase Government budget, use of innovative financing strategies, and health insurance, complemented with enhanced program efficiency. [ABSTRACT FROM AUTHOR]

Uncertainty surrounding the risk of developing and dying from Thrombosis and Thrombocytopenia Syndrome (TTS) associated with the AstraZeneca (AZ) COVID-19 vaccine may contribute to vaccine hesitancy. A model is urgently needed to combine and effectively communicate evidence on the risks versus benefits of the AZ vaccine. We developed a Bayesian network to consolidate evidence on risks and benefits of the AZ vaccine, and parameterised the model using data from a range of empirical studies, government reports, and expert advisory groups. Expert judgement was used to interpret the available evidence and determine the model structure, relevant variables, data for inclusion, and how these data were used to inform the model. The model can be used as a decision-support tool to generate scenarios based on age, sex, virus variant and community transmission rates, making it useful for individuals, clinicians, and researchers to assess the chances of different health outcomes. Model outputs include the risk of dying from TTS following the AZ COVID-19 vaccine, the risk of dying from COVID-19 or COVID-19-associated atypical severe blood clots under different scenarios. Although the model is focused on Australia, it can be adapted to international settings by re-parameterising it with local data. This paper provides detailed description of the model-building methodology, which can be used to expand the scope of the model to include other COVID-19 vaccines, booster doses, comorbidities and other health outcomes (e.g., long COVID) to ensure the model remains relevant in the face of constantly changing discussion on risks versus benefits of COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Improving vaccine procurement performance has been a priority concern of national health authorities in the Middle East and North Africa (MENA) region for years particularly in terms of its role in accessing new vaccines and assuring a steady supply of quality vaccines at affordable prices. This article reviews the vaccine procurement mechanisms in the MENA region; analyzes the factors and drivers affecting demand for and supply of vaccines; discusses the main challenges; and suggests measures which can increase efficiency gains and generate the budgetary room to introduce life-saving vaccines. Based on in-depth analysis of available data and interviews with key informants at the regional and country level, this paper explains why most of the current strategies do not sufficiently recognize the specific characteristics of vaccine markets and best practices in procurement given these markets. The paper suggests potential efficiency gains for governments and global partners from pooling demand and moving from transaction-based purchasing to strategic purchasing in order to strengthen immunization services and introduce more life-saving vaccines. [ABSTRACT FROM AUTHOR]

Abstract Clinical trials covering the immunogenicity of a vaccine aim to study the longitudinal dynamics of certain immune cells after vaccination. The corresponding immunogenicity datasets are mainly analyzed by the use of statistical (mixed effects) models. This paper proposes the use of mathematical ordinary differential equation (ODE) models, combined with a mixed effects approach. ODE models are capable of translating underlying immunological post vaccination processes into mathematical formulas thereby enabling a testable data analysis. Mixed models include both population-averaged parameters (fixed effects) and individual-specific parameters (random effects) for dealing with inter- and intra-individual variability, respectively. This paper models B-cell and T-cell datasets of a phase I/II, open-label, randomized, parallel-group study (NCT00492648) in which the immunogenicity of a new Herpes Zoster vaccine (Shingrix) is compared with the original Varicella Zoster Virus vaccine (Varilrix). Since few significant correlations were found between the B-cell and T-cell datasets, each dataset was modeled separately. By following a general approach to both the formulation of several different models and the procedure of selecting the most suitable model, we were able to propose a mathematical ODE mixed-effects model for each dataset. As such, the use of ODE-based mixed effects models offers a suitable framework for handling longitudinal vaccine immunogenicity data. Moreover, this approach allows testing for differences in immunological processes between vaccines or schedules. We found that the Shingrix vaccination schedule led to a more pronounced proliferation of T-cells, without a difference in T-cell decay rate compared to the Varilrix vaccination schedule. [ABSTRACT FROM AUTHOR]

Highlights • Explores anecdotal evidence that grandparents could influence paediatric vaccine uptake. • Reviews articles that suggest grandparents influence parents' decision to vaccinate children. • Currently there is no direct evidence that grandparents influence parents' vaccination decisions. • Articles reviewed highlight indirect evidence of grandparental influence on parents' decisions. • Highlights grandparents' attitudes and beliefs are echoed in parents' decision to vaccinate. Abstract The global reduction in childhood infectious diseases since the 1960s is primarily due to the success of extensive worldwide immunisation campaigns. However, the universal vaccination coverage program appears to have lost momentum in the wake of negative, unfounded claims about the safety of vaccines. While parents of the 21st century have little first-hand knowledge of devastating childhood diseases, grandparents are more likely to remember family and community members who were afflicted. In the current age of vaccine hesitancy and science scepticism, where research-informed arguments are not always persuasive, grandparents, through their experience of the diseases, may positively influence paediatric vaccine uptake. This paper reviews the literature investigating potential direct or indirect influences of grandparents on parents' decisions to vaccinate their children. A database search using the keywords immunisation , vaccination , children and grandparents resulted in 1988 articles. Titles were screened for relevance and seventy-seven results were retained. After the abstracts were read, only five articles that either explored paediatric vaccines, factors promoting and/or inhibiting paediatric vaccine use and decision-making strategies were reviewed. One paper located through Google Scholar, which failed to show up on database searches, was also retained for a total of six papers. While none of the six papers set out to explore the impact of grandparents on vaccine uptake, they found that grandparents were involved to varying degrees in paediatric vaccine uptake within young families. The research clearly showing that grandparents, and older people more generally, promote vaccination uptake is not currently available. The dearth of literature shows the need for research exploring the perceived and real influences of grandparents on childhood vaccination. This will establish whether grandparents' memory and knowledge of preventable childhood infectious diseases could be harnessed as a public health measure to counteract the current, ill-informed, negative attention on paediatric vaccines. [ABSTRACT FROM AUTHOR]

• OMVs from Bordetella bronchiseptica elicit immune responses in macrophages. • Host Defense Peptides modulate the immune responses differently for sOMV and hOMVs. • Signaling via human TLRs hTLR2, hTLR4, hTLR5 and hTLR9 is stimulated by OMVs. • hTLR2- and hTLR4-mediated signaling can be downregulated by LL-37 and K9CATH. • Uptake of OMVs plays a minimal role in eliciting an immune response in macrophages. Antibiotic resistance is increasing and one strategy to prevent resistance development is the use of bacterial vaccines. For Gram-negative bacteria, natural outer membrane vesicles (OMVs) could be used for vaccine development. These vesicular structures are naturally produced by all Gram-negative bacteria and contain several antigens in their native environment. However, despite that the presence of lipopolysaccharide (LPS) may aid as intrinsic adjuvant, there is a risk that it may also cause undesired immune responses. Therefore, molecules to dampen LPS-induced toll-like receptor (TLR) 4 activation may be needed. Here host defense peptides (HDPs), like cathelicidins, can play an important role. They have been shown to interact with LPS and thereby neutralize LPS-induced TLR4 activation. However, there is currently no knowledge about neutralization in an OMV-based setting. Therefore, in this paper the immune modulating capacity of HDPs was investigated after macrophage stimulation with either spontaneous or heat-induced B. bronchiseptica OMVs. This revealed that the cathelicidins LL-37, CATH-2, PMAP-36 and K9CATH were able to modulate immune responses. Interestingly, immune modulation by these cathelicidins was different for spontaneous compared to heat-induced OMVs. Interaction studies revealed that the mode of binding of cathelicidins to OMVs slightly differed between OMV classes. Furthermore, TLR screening revealed that TLR2, 4, 5 and 9 were involved in stimulation of macrophages by OMVs, with TLR4-mediated activation being the most important pathway. Uptake of OMVs did not play a major role in macrophage activation. Taken together, this study shows how OMVs can activate macrophages and how cathelicidins may modulate these immune responses. [ABSTRACT FROM AUTHOR]

The introduction of the Human papillomavirus (HPV) vaccine has shown potential to not only prevent cervical cancer but also drive adolescents' access to other health care services, even in low-income countries. Few studies have been conducted to date to identify best practices and estimate the acceptance, operational challenges and benefits of including broader adolescent health interventions into immunization efforts, knowledge which is essential to supporting widespread integration. In this paper we review the efforts undertaken by the government of Togo to integrate adolescent health programming with the HPV vaccination roll out. With the support of partners (GAVI, WHO, UNFPA and UNICEF), the country successfully completed, in 2017, two years of an HPV vaccine demonstration project, which entailed vaccinating 10-year-old girls against HPV in two selected districts of the country and integrating a health education component focused on puberty education / menstrual hygiene and hand washing practice. Our study is a post-implementation program evaluation, using mixed methods to assess key questions of feasibility and acceptability of an integrated adolescent package of care. It showed that the HPV vaccination in conjunction with the health education sessions was well received by the majority of health care providers, teachers and parents. Our study confirmed that in Togo it proved feasible to combine education and HPV vaccination in school-based service delivery. However, more operational research is neded to understand how to increase the impact and sustainability of the co-delivery of interventions. We did not analyze the health impact and cost implications of the intervention, which will be an important consideration for scaling up such integration efforts alongside routine immunization. [ABSTRACT FROM AUTHOR]

A WHO global strategy launched in November 2020 sets out an ambitious pathway towards the worldwide elimination of cervical cancer as a public health problem within the next 100 years. Achieving this goal will require investment in innovative approaches. This review aims to describe integrated approaches that combine human papillomavirus (HPV) vaccination and cervical cancer screening in low- and middle-income countries (LMIC), and their efficacy in increasing uptake of services. A systematic review was conducted analyzing relevant papers from Embase, Medline, CINAHL and CAB Global Health databases, as well as grey literature. Narrative synthesis was performed on the included studies. Meta-analysis was not appropriate due to the heterogeneity and nature of included studies. From 5,278 titles screened, 11 uncontrolled intervention studies from four countries (from Africa and east Asia) were included, all from the past 12 years. Four distinct typologies of integration emerged that either increased awareness of HPV and/or cervical cancer screening, and/or coupled the delivery of HPV vaccination and cervical cancer screening programs. The synthesis of findings suggests that existing HPV vaccination programs can be a useful pathway for educating mothers and other female caregivers about cervical cancer screening; through in person conversations with care providers (preferred) or take-home communications products. Integrated service delivery through outreach and mobile clinics may overcome geographic and economic barriers to access for both HPV vaccination and cervical cancer screening, however these require significant program and system resources. One study promoted HPV vaccination as part of integrated service delivery, but there were no other examples found that examined use of cervical cancer screening platforms to promote or educate on HPV vaccination. This review has demonstrated gaps in published literature on attempts to integrate HPV vaccination and cervical cancer screening. The most promising practices to date seem to relate to integrated health communications for cervical cancer prevention. Future research should further explore the opportunities for integrated health communications to support the efforts towards the new global cervical cancer elimination agenda, and costs and feasibility of integrated service delivery for underserved populations. [ABSTRACT FROM AUTHOR]