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Seasonal influenza has a significant impact on global public health each year, especially in older adults 65 years of age and above. This paper presents the evolution of high-dose influenza vaccine and the quantity as well as quality of evidence on this vaccine. Its introduces other peer-reviewed manuscripts included in this supplement covering the benefits high-dose influenza vaccine over ten consecutive influenza seasons. The development of the high-dose influenza vaccine represents an important step in the evolution of influenza vaccines, offering an advancement in prevention of influenza and a step in encouraging healthy aging in older adults. A video summary of the article can be accessed via the Supplementary data link at the end of this article.

Objective To develop and evaluate a paper-based point-of-care HPV serology test to determine if an individual has received two or more HPV immunizations. Methods The paper-based immunoassay was constructed using a nitrocellulose lateral flow strip with adsorbed HPV16 virus-like particles serving as the capturing moiety. Three capture zones containing virus-like particles were placed in series to allow for visual discrimination between high and low HPV16 plasma antibody concentrations. A plasma separation membrane was used to allow whole blood to be applied directly to the assay. All reagents were dried on glass fiber pads during device fabrication and were rehydrated with buffer at the time of use. A pilot study consisting of 35 subjects with a history of zero, one, two or three HPV vaccines was conducted to evaluate the immunoassay. The completed paper-based immunoassays were scanned for visual interpretation by three researchers who were blinded to the true results and separately evaluated quantitatively using MATLAB. Results For the 28 tests valid for analysis, fifteen subjects reported receiving two or more HPV vaccines, three reported receiving one, and ten reported having no HPV vaccinations. The paper-based immunoassays for all fifteen subjects who reported having received two or more HPV vaccines were judged positive by all researchers. Twelve of the thirteen tests from individuals reporting one or zero vaccinations were deemed negative by all observers. One test from an unvaccinated individual was judged positive by two out of three reviewers. Quantitatively, all tests were correctly separated between the two groups. Conclusions We successfully designed and tested a HPV serology test amenable to the point-of-care. The device showed promising results in a pilot study for discriminating between those who received two or more HPV vaccinations and those who did not. Furthermore, this device offers a platform for producing other semi-quantitative point-of-care serological tests.

Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children.

In 2012, the World Health Organization (WHO) released a position paper on influenza vaccination recommending that pregnant women have the highest priority for seasonal vaccination in countries where the initiation or expansion of influenza immunization programs is under consideration. Although the primary goal of the WHO recommendation is to prevent influenza illness in pregnant women, the potential benefits of maternal immunization in protecting young infants are also recognized. The extent to which maternal influenza vaccination may prevent adverse birth outcomes such as preterm birth or small-for-gestational-age birth, however, is unclear as available studies are in disagreement. To inform WHO about the empirical evidence relating to possible benefits of influenza vaccination on birth outcomes, a consultation of experts was held in Montreal, Canada, September 30–October 1, 2015. Presentations and discussions covered a broad range of issues, including influenza virus infection during pregnancy and its effect on the health of the mother and the fetus, possible biological mechanisms for adverse birth outcomes following maternal influenza illness, evidence on birth outcomes following influenza illness during pregnancy, evidence from both observational studies and randomized controlled trials on birth outcomes following influenza vaccination of pregnant women, and methodological issues. This report provides an overview of the presentations, discussions and conclusions.

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.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. The Modified Vaccinia Ankara (MVA) vector system is being explored as a platform for development of multiple vaccines. This paper reviews the molecular and biological features specifically of the MVA-BN vector system, followed by a template with details on the safety and characteristics of an MVA-BN based vaccine against Zaire ebolavirus and other filovirus strains. The MVA-BN-Filo vaccine is based on a live, highly attenuated poxviral vector incapable of replicating in human cells and encodes glycoproteins of Ebola virus Zaire, Sudan virus and Marburg virus and the nucleoprotein of the Thai Forest virus. This vaccine has been approved in the European Union in July 2020 as part of a heterologous Ebola vaccination regimen. The MVA-BN vector is attenuated following over 500 serial passages in eggs, showing restricted host tropism and incompetence to replicate in human cells. MVA has six major deletions and other mutations of genes outside these deletions, which all contribute to the replication deficiency in human and other mammalian cells. Attenuation of MVA-BN was demonstrated by safe administration in immunocompromised mice and non-human primates. In multiple clinical trials with the MVA-BN backbone, more than 7800 participants have been vaccinated, demonstrating a safety profile consistent with other licensed, modern vaccines. MVA-BN has been approved as smallpox vaccine in Europe and Canada in 2013, and as smallpox and monkeypox vaccine in the US in 2019. No signal for inflammatory cardiac disorders was identified throughout the MVA-BN development program. This is in sharp contrast to the older, replicating vaccinia smallpox vaccines, which have a known risk for myocarditis and/or pericarditis in up to 1 in 200 vaccinees. MVA-BN-Filo as part of a heterologous Ebola vaccination regimen (Ad26.ZEBOV/MVA-BN-Filo) has undergone clinical testing including Phase III in West Africa and is currently in use in large scale vaccination studies in Central African countries. This paper provides a comprehensive picture of the MVA-BN vector, which has reached regulatory approvals, both as MVA-BN backbone for smallpox/monkeypox, as well as for the MVA-BN-Filo construct as part of an Ebola vaccination regimen, and therefore aims to provide solutions to prevent disease from high-consequence human pathogens.

In high-income countries, there is an increased tendency to replace inactivated seasonal trivalent influenza (TIV) vaccines with quadrivalent (QIV) vaccines as these are considered to give a greater public health benefit. In addition, several recent studies from the USA and Europe indicate that replacement with QIV might also be cost-effective; however, the situation in low- and middle-income countries (LMIC) is less clear as few studies have investigated this aspect. The paper by de Boer et al. (2008) describes a dynamic modelling study commissioned by WHO that suggests that in LMICs, under certain conditions, QIV might also be more cost-effective than TIV. In this commentary, we discuss some important aspects that policymakers in LMICs might wish to take into account when considering replacing TIV by QIV. Indeed, from the data presented in the paper by de Boer et al. it can be inferred that replacing QIV for TIV would mean a 25-29% budget increase for seasonal influenza vaccination in South Africa and Vietnam, resulting in an incremental influenza-related health impact reduction of only 7-8% when a 10% symptomatic attack rate is assumed. We argue that national health budget considerations in LMIC might lead decision-makers to choose other investments with higher health impact for a budget equivalent to roughly a quarter of the yearly TIV immunization costs. In addition to an increased annual cost that would be associated with a decision to replace TIV with QIV, there would be an increased pressure on manufacturers to produce QIV in time for the influenza season requiring manufacturers to produce some components of the seasonal vaccine at risk prior to the WHO recommendations for influenza vaccines. Unless the current uncertainties, impracticalities and increased costs associated with QIVs are resolved, TIVs are likely to remain the more attractive option for many LMICs. Each country should establish its context-specific process for decision-making based on national data on disease burden and costs in order to determine whether the health gains out-weigh the additional cost of moving to QIV. For example, immunizing more people in the population, especially those in higher risk groups, with TIV might not only provide better value for money but also deliver better health outcomes in LMICs. Countries with local influenza vaccine manufacturing capacity should include in their seasonal influenza vaccine procurement process an analysis of the pros- and cons- of TIV versus QIV, to ensure both feasibility and sustainability of local manufacturing.

A high level of concern is placed on the storage, handling, transportation, and distribution of vaccines and other pharmaceutical products, particularly those that are time and temperature sensitive. While active and passive cooling equipment and monitoring devices are important, it is the various personnel responsible for executing and writing procedures, designing and operating systems, and investigating problems and helping prevent them who are paramount in establishing and maintaining a "cold chain" for time and temperature sensitive pharmaceutical products (TTSPPs). These professionals must possess the required competencies, knowledge, skills and abilities so they can effectively perform these activities with appropriate levels of expertise. These are complex tasks that require the development of higher cognitive skills that cannot be adequately addressed through professional development opportunities based on simple information delivery and content acquisition. This paper describes two unique learning solutions (one on a bus called the "wheels course" and the other online called "e-learning") that have been developed by WHO Global Learning Opportunities (WHO/GLO) to provide participants with opportunities not just to learn about cold chain systems or vaccine management, but, rather, to develop high levels of expertise in their respective fields through experiential and authentic learning activities. In these interactive learning environments, participants have opportunities to address real-life situations in contexts similar to what they may face in their own work environments and develop solutions and critical thinking skills they can apply when they return to their jobs. This paper further delineates the managerial and operational vaccine management functions encompassed in these two unique learning environments. The paper also describes the alignment of the objectives addressed in the "wheels course" and the e-learning version with effective vaccine management (EVM) criteria as prescribed by WHO. The paper concludes with an example of a real world product developed by course graduates (specifically a decision tree that is now used by some national programmes). These types of products, valuable in their own right, often emerge when learning environments based on authentic learning principles are designed and implemented as they were by WHO/GLO.

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.

Background Dengue fever is one of the most rapidly advancing viral vector-borne diseases worldwide and vaccine candidates are in the final stages of clinical trials, representing a decisive opportunity to control the disease. To decide whether and where to support the introduction of new vaccines it is crucial to assess costs imposed by the disease and cost-effectiveness of vaccine programmes. Objective To identify economic evidence about dengue fever immunization, by systematic review, to assist future policy decisions and investment. Methods The electronic search stage was conducted on PubMed/Medline, Embase, Web of Science, Global Health, NHS Economic Evaluation Database (NHS EED) and Latin American and Caribbean Health Sciences Literature (LILACS) databases. Searches were restricted to papers published between January 1970 and February 2016. Selected papers were quality assessed using three recognized checklists. Results Eleven relevant studies were identified and there is economic evidence of a satisfactory quality level, derived through modelling approaches, to conclude that dengue fever vaccines will be economically advantageous when compared to vector preventive strategies, despite uncertainties surrounding vaccine efficacy and costs per vaccine dose. Quality assessment based on checklists showed similar findings and although overall quality was considered satisfactory, there were relevant methodological issues not considered among studies reviewed. Conclusion Several uncertainties still remain about effectiveness of dengue fever vaccines; however, the reviewed economic evidence suggests that, when available, the vaccine can be economically advantageous at moderate prices. Future research needs to confirm findings from the economic models by using actual costs and effectiveness data.

Vaccine effectiveness (VE) studies provide a measure of population-based vaccine performance by combining immunization history data with rates of disease incidence. This review assessed the feasibility of using electronic immunization registry data sources in VE studies. Electronic databases were searched through January 31, 2010. Out of 17 studies, only one paper assessed data accuracy (71%), and three papers assessed population coverage of the registry (estimates ranged from 25% to 90%). This review shows that registry-based data sources can be used to conduct VE studies in a variety of settings and populations. However, we found little information regarding the quality of this data source in VE studies and future evaluations should investigate their reliability, accuracy, and potential bias.

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.

The benefits of vaccines have been centred on their specific effects on subsequent infections by target pathogens. Recent studies, however, have opened up new insights into additional effects of vaccines known as non-specific effects (NSEs) or heterologous effects of vaccines. While several articles have reviewed epidemiological and immunological evidence for NSEs of vaccines in humans, similar works on veterinary vaccines are scarce. The objective of this paper was to review the findings of published studies on NSEs of vaccines developed or repurposed for use in animals. In total 8412 titles were retrieved from PubMed and CABI databases on the 30th of April 2021. After the final stage of screening, 45 eligible articles were included in the review. Data from these articles were summarised and presented here. In general, most of the vaccines studied in the reviewed articles have beneficial NSEs against multiple pathogens and disease conditions. There were, however, fewe studies reporting detrimental NSEs from both non-live and live vaccines which is in contrast to the currently existing evidence of beneficial NSEs of live vaccines and detrimental NSEs of non-live vaccines. This review may be used as a complement for future review of RCT studies of NSEs of vaccines in animals and provide a useful addition to the evolving understanding of the NSEs of vaccines.

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.

The paper describes how the Advisory Committee on Communicable Diseases (ACCD) in Sri Lanka addresses new challenges by ensuring participatory, collective and transparent decision-making through a broad representation of stakeholders. The Committee, which is more than 40 years old, differs from many other national immunization advisory committees, since it has a broad mandate to deal with all communicable diseases, including those for which there are no vaccines, and addresses such areas as disease surveillance and health system improvements, in addition to vaccination-related issues. The Committee has 38 members. Unlike in some countries, ACCD recommendations are legally binding for all public sector health providers. The paper provides several examples of recent recommendations and factors that influenced the Committee's decision-making, and concludes with ways the Committee can be improved.

Infectious diseases may cause serious morbidity and mortality in pregnant women, their foetuses, and infants; the risk associated with any newly emerging infectious disease (EID) is likely unknown at the time of its emergence. While the ongoing SARS-CoV-2 pandemic shows that the development of vaccines against new pathogens can be considerably accelerated, the immunization of pregnant women generally lags behind the general population. Guided by the priority pathogen list for WHO’s R&D Blueprint for Action to Prevent Epidemics, this workshop sought to define the evidence needed for use of vaccines against EIDs in pregnant and lactating women, using Lassa fever as a model. Close to 60 maternal immunization (MI) and vaccine safety experts, regulators, vaccine developers, Lassa fever experts, and investigators from Lassa-affected countries examined the critical steps for vaccine development and immunization decisions for pregnant and lactating women. This paper reports on key themes and recommendations from the workshop. Current practice still assumes the exclusion of pregnant women from early vaccine trials. A shift in paradigm is needed to progress towards initial inclusion of pregnant women in Phase 2 and 3 trials. Several practical avenues were delineated. Participants agreed that vaccine platforms should be assessed early for their suitability for maternal immunization. It was noted that, in some cases, nonclinical data derived from assessing a given platform using other antigens may be adequate evidence to proceed to a first clinical evaluation and that concurrence from regulators may be sought with supporting rationale. For clinical trials, essential prerequisites such as documenting the disease burden in pregnant women, study site infrastructure, capabilities, and staff experience were noted. Early and sustained communication with the local community was considered paramount in any program for the conduct of MI trials and planned vaccine introduction.

Background Pneumococcal vaccines have been developed to protect infants and young children from pneumococcal diseases. Vaccination coverage studies are important in determining a population’s vaccination status and strategically adjusting national immunization programs (NIP). In this paper, we aim to describe the coverage of pneumococcal conjugate vaccines (PCVs) immunization for birth cohorts from 2012 to 2020 and discussed the factors influencing the coverage. Methods Vaccination data were collected via the vaccination information database in Shanghai, China, for children born from 2012 to 2020. The population data used in this study were collected from each community from 2012 to 2020. The coverage of initial immunization (1st dose), basic immunization (three doses) and full immunization (3 + 1 doses) for PCVs was calculated according to the number of doses received. As vaccination coverage was assessed each year, Annual Growth Rate (AGR) was used to describe the variation trend of vaccination coverage. Immunization time and completeness of different PCVs were also analyzed. Results The total number of births from 2012 to 2020 was 38,268 in Huangpu District, Shanghai, China. The initial immunization coverage of PCVs increased from 12.26% in 2012 to 49.65% in 2020, and the highest coverage was 50.61% in 2019. The cumulative vaccination coverage of PCVs was 19.4% for initial immunization and 16.8% for basic immunization from 2012 to 2020. And cumulative full immunization coverage of PCVs was 12.3% from 2012 to 2019. The PCVs coverage of most vaccination statuses showed an obvious upward trend from 2017 to 2020. Conclusions Despite an upward trend in vaccination coverage of PCVs, the vaccination coverage of initial, basic and full immunization among children is still low. And given the heavy burden of Streptococcus pneumoniae (Sp) among children in China and the fact that the current vaccination coverage cannot effectively protect children, it is recommended that the government include PCVs into the NIP as soon as possible.

Background Maternal immunization rates and vaccine uptake in Latin America vary from country to country. This variability stems from factors related to pregnant women, vaccine recommendations from healthcare providers and the health system. The aim of this paper is to describe women’s knowledge and attitudes to maternal immunziation, and barriers to access and vaccination related decision-making processes in Latin American countries. Methods We conducted focus group discussions (FGD) with pregnant women in five middle-income countries: Argentina, Brazil, Honduras, Mexico and Peru, between July 2016 and July 2018. The FGDs were conducted by trained qualitative researchers in diverse clinics located in the capital cities of these countries. Results A total of 162 pregnant women participated in the FGDs. In general, participants were aware of the recommendation to receive vaccines during pregnancy but lacked knowledge regarding the diseases prevented by these vaccines. Pregnant women expressed a desire for clearer and more detailed communication on maternal vaccines by their healthcare professionals instead of relying on other sources of information such as the internet. Overall, participants had positive attitudes towards maternal immunization and were open to receiving vaccines in pregnancy based on general trust they have in recommendations made by their healthcare providers. The main obstacles pregnant women said they encounter were mainly centered around their clinical experience: long waiting times, vaccine shortages, and impolite behavior of healthcare providers or clinical staff. Conclusion Important advances have been made in Latin America to promote maternal immunization. Results from this study show that an important aspect that remains to be addressed, and is crucial in improving vaccine uptake in pregnancy, is women’s clinical experience. We recommend pregnant women to be treated as a priority population for providing immunization and related healthcare education. It is imperative to train healthcare providers in health communication so they can effectively communicate with pregnant women regarding maternal vaccines and can fill knowledge gaps that otherwise might be covered by unreliable sources dispensing inaccurate information.

International audience; For over 100 years, large epidemics of meningococcal meningitis have occurred every few years in areas of the African Sahel and sub-Sahel known as the African meningitis belt. Until recently, the main approach to the control of these epidemics has been reactive vaccination with a polysaccharide vaccine after an outbreak has reached a defined threshold and provision of easy access to effective treatment but this approach has not prevented the occurrence of new epidemics. Meningococcal conjugate vaccines, which can prevent meningococcal carriage and thus interrupt transmission, may be more effective than polysaccharide vaccines at preventing epidemics. Because the majority of African epidemics have been caused by serogroup A meningococci, a serogroup A polysaccharide/tetanus toxoid protein conjugate vaccine (PsA-TT) has recently been developed. Results from an initial evaluation of the impact of this vaccine on meningococcal disease and meningococcal carriage in Burkina Faso have been encouraging. To review how the research agenda for meningococcal disease in Africa has been changed by the advent of PsA-TT and to define a new set of research priorities for study of meningococcal infection in Africa, a meeting of 41 scientists was held in Dakar, Senegal on April 24th and 25th 2012. The research recommendations developed during the course of this meeting are presented in this paper. The need for enhanced surveillance for meningitis in defined populations with good diagnostic facilities in African countries at risk of epidemics was identified as the highest priority. This is needed to determine the duration of protection against serogroup A meningococcal disease provided by PsA-TT and to determine the risk of disease and carriage caused by meningococci of other serogroups. Other research areas given high priority included identification and validation of serological correlates of protection against meningococcal disease and carriage, development of improved methods for detecting carriage and epidemiological studies aimed at determining the reasons underlying the peculiar epidemiology of meningococcal disease in the African meningitis belt. Minutes and working papers from the meeting are provided in supplementary tables and some of the presentations made at the meeting are available on the MenAfriCar consortium website (www.menafricar.org) and on the web site of the Centers for Disease Control (www.cdc.gov).Conference report - Dakar discussion group on priorities for research on epidemic meningococcal disease in Africa

BACKGROUND: Achieving universal immunization coverage and reaching every child with life-saving vaccines will require the implementation of pro-equity immunization strategies, especially in poorer countries. Gavi-supported countries continue to implement and report strategies that aim to address implementation challenges and improve equity. This paper summarizes the first mapping of these strategies from country reports. METHODS: Thirteen Gavi-supported countries were purposively selected with emphasis on Gavi's priority countries. Following a scoping of different documents submitted to Gavi by countries, 47 Gavi Joint Appraisals (JAs) for the period 2016-2019 from the 13 selected countries were included in the mapping. We used a consolidated framework synthesized from 16 different equity and health systems frameworks, which incorporated UNICEF's coverage and equity assessment approach - an adaptation of the Tanahashi model. Using search terms, the mapping was conducted using a combination of manual search and the MAXQDA qualitative analysis tool. Pro-equity strategies meeting the inclusion criteria were identified and compiled in an Excel database, and then populated on a tableau visualization dashboard. RESULTS: In total, 258 pro-equity strategies were implemented by the 13 sampled Gavi-supported countries between 2016 and 2019. The framework determinants of social norms, utilization, and management and coordination accounted for more than three-quarters of all pro-equity strategies implemented in these countries. The median number of strategies reported per country was 17. Afghanistan, Nigeria, and Uganda reported the highest number of strategies that we considered as pro-equity. CONCLUSION: Findings from this mapping can be useful in addressing equity gaps, reaching partially immunized, and 'zero-dose' vaccinated children, and valuable resource for countries planning to implement pro-equity strategies, especially as immunization stakeholders reimagine immunization delivery in light of COVID-19, and as Gavi finalizes its fifth organizational strategy. Future efforts should seek to identify pro-equity strategies being implemented across additional countries, and to assess the extent to which these strategies have improved immunization coverage and equity.

Background and objectives Public concern about an unsubstantiated link between MMR vaccine and autism stemmed from a 1998 paper by Dr Andrew Wakefield and colleagues, and the substantial media coverage which that work attracted. Though the Wakefield paper is now discredited and an MMR-autism link has never been demonstrated empirically, this concern has manifested in over a decade of suboptimal MMR uptake. Few qualitative studies have explored parents’ MMR decision-making since uptake began to improve in 2004. This study updates and adds methodological rigour to the evidence base. Methods 24 mothers planning to accept, postpone or decline the first MMR dose (MMR1) for their 11–36 month-old children, described their decision-making in semi-structured interviews. Mothers were recruited via General Practice, parents’ groups/online forums, and chain referral. MMR1 status was obtained from General Practice records 6 months post-interview. Interview transcripts were coded and interpreted using a modified Grounded Theory approach. Results Five themes were identified: MMR vaccine and controversy; Social and personal consequences of MMR decision; Health professionals and policy; Severity and prevalence of measles, mumps and rubella infections; Information about MMR and alternatives. Results indicated that MMR1 acceptors were sympathetic toward Wakefield as a person, but universally rejected his study which sparked the controversy; parents opting for single vaccines expressed the sense that immune overload is not a consideration but that not all three components of MMR are warranted by disease severity; and MMR1 rejectors openly criticised other parents’ MMR decisions and decision-making. Conclusions This study corroborated some previous qualitative work but indicated that the shrinking group of parents now rejecting MMR comprises mainly those with more extreme and complex anti-immunisation views, whilst parents opting for single vaccines may use second-hand information about the controversy. In response, policymakers and practitioners should revise their expectations of today's MMR decision-makers, and their methods for supporting them.

This paper describes British efforts to map the Russian influenza outbreaks of the early 1890s and describe the timing and course of the epidemic waves. Drawing on two surveys conducted by Britain's Local Government Board (LGB), the paper shows how, in a pre-virological era, the board was able to establish that influenza was an intensely infectious disease. Its key observation, however, was that Russian influenza had taken the form of three, and possibly four, distinct waves of infection, with the second wave in the spring of 1891 proving more lethal than the first wave, and the third wave in the winter of 1892 proving almost as lethal again. Most of this mortality was due to excess deaths from respiratory disease, particularly in the middle age ranges, but while these insights could and, arguably, should have aided the public health response, British health authorities preferred to advocate cautious preventive measures that did little to alleviate the pandemic's impact. The policy would prove especially costly in 1918-1919 when the LGB missed the opportunity to provide extra nursing cover for influenza convalescents following the initial summer wave of the 1918 Spanish influenza pandemic.

Vaccination plays an important role in pandemic planning and response. The possibility of developing an effective vaccine for a novel pandemic virus is not assured. However, as we have seen with SARS-CoV-2 vaccine development, with sufficient resources and global focus, successful outcomes can be achieved in a relatively short period. However even when vaccine is available it will initially be scarce. When one becomes available, how should it be distributed? In this paper we explicate how ethical thinking that is carefully attuned to context is essential to decisions about how we should conduct vaccination in a pandemic where demand exceeds supply. We focus on two key issues. First, setting the aims for a pandemic vaccination programme. Second, thinking about the means of delivering a chosen aim. We outline how pandemic vaccine distribution strategies can be implemented with distinct aims, e.g. protecting groups at greater risk of harm, saving the most lives, or ensuring societal benefit. Each aim will result in a focus on a different priority population and each strategy will have a different benefit-harm profile. Once we have decided our aim, we still have choices to make about delivery. We may achieve at least some ends via direct or indirect strategies. Such policy decisions are not merely technical, but necessarily involve ethics. One important general issue is that such planning decisions about distribution will always be made under conditions of uncertainty about vaccine safety and effectiveness. However, planning how to distribute vaccine for SARS-CoV-2 is even harder because we understand relatively little about the virus, transmission, and its immunological impact in the short and long term.

This issue of Vaccine is devoted to papers from a research project that developed two types of simulation models, static and dynamic transmission, to evaluate the cost-effectiveness of maternal immunization to prevent pertussis in infants in low- and middle-income countries (LMICs). The research was conducted by a multinational team of investigators and funded by the Bill & Melinda Gates Foundation to gain an understanding of when and where maternal immunization might be a good public health investment for LMICs. Here we review the project’s central lessons for vaccine policy and research. Models require a lot of data. As most LMICs lack good data, the models were built using pertussis disease burden data from Brazil, a middle-income country with three long-established, independent information systems (disease surveillance, hospitalization, and mortality), on the hypothesis that the disease process is similar across countries. Values for key parameters, particularly infant mortality, infant vaccine coverage, and costs of vaccination and treatment, were then varied to represent other LMICs. The results show that coverage levels of infant whole cell pertussis (wP) vaccine are key to the cost-effectiveness of maternal pertussis immunization. In settings where infant wP coverage is below the threshold thought necessary to eliminate pertussis in the population, 90–95%, maternal immunization is cost-effective, even cost-saving. By contrast, it is very expensive in countries capable of maintaining infant vaccination in or above the threshold range. The research also suggests that, while static models may serve to explore an intervention’s cost-effectiveness initially, dynamic transmission models are essential for more accurate estimates. These findings can help guide policies toward maternal pertussis immunization, but also show that developing better data on neonatal pertussis mortality burden and infant vaccine coverage in LMICs, and on the duration of immunity of currently available pertussis vaccines, are key priorities to support better vaccine policy.

Highlights • Dynamic transmission models of infectious disease capture the herd immunity effects of vaccination. • We compared dynamic and static models of maternal acellular pertussis (aP) immunization built with Brazilian data. • At infant vaccine coverage 90–95%. • The background effect of routine infant vaccination is critical to the cost-effectiveness of maternal aP immunization., Background This paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile. Methods We defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models’ different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated. Results The dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90–95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models’ estimates over their different time horizons are compared at infant coverage

COVID-19 vaccines are new brands of consumer health technology being introduced to the market. Considering consumer behaviour approaches in this time of crisis, the risk of vaccine hesitancy, the call for more transparency and effective messaging to gain trust, and equitable distribution of this vaccine, this is unexplored theoretical terrain. This commentary takes a multidisciplinary approach to understand and theoretically explore the marketing, distribution, and acceptance of the COVID-19 vaccine. The paper integrates marketing principles, including advertisement and branding of consumer health technology with supply chain management, public affairs, and public health. A theoretical framework was presented to illustrate this relationship and key areas of concerns. The practical implications relevant to equity, ethics, education, employment, and the economic impact was presented.

While a human challenge study holds the prospect of accelerating the development of a vaccine for the coronavirus SARS-CoV-2, it may be opposed due to risks of harm to participants and researchers. Given the increasing number of human deaths and severe disruption to lives worldwide, we argue that a SARS-CoV-2 challenge study is ethically justifiable as its social value substantially outweighs the risks. Such a study should therefore be seriously considered as part of the global research response towards the COVID-19 pandemic. In this paper, we contribute to the debate by addressing the misperception that a challenge study for the coronavirus would lower scientific and ethical standards for vaccine research and development, and examine how it could be ethically conducted. We also set out information that needs to be disclosed to prospective participants to obtain their consent.

Cholera-endemic Eastern India has played an important role in the development of oral cholera vaccines (OCV) through conduct of pivotal trials in Kolkata which led to the registration of the first low-cost bivalent killed whole cell OCV in India in 2009, and subsequent prequalification by the World Health Organization prequalification in 2011. Odisha hosted an influential early demonstration project for use of the vaccine in a high-risk population and provided data and lessons that were crucial input in the Vaccine Investment Strategy developed by Gavi, the Vaccine Alliance in 2013. With Gavi's decision to finance an OCV stockpile, the demand for OCV surged and vaccine has been deployed with great success worldwide in areas of need in response to outbreaks and disasters, most notably in Africa. However, although India is considered one of the highest burden countries, no further use of OCV has occurred since the demonstration project in Odisha in 2011. In this paper we will summarize the important contributions of India to the development and use of OCV and discuss the possible barriers to OCV introduction as a public health tool to control cholera.

Objectives To determine the effectiveness of influenza vaccination during pregnancy on child health outcomes. Design Systematic review/meta-analysis. Data sources Clinical Trials.gov, Cochrane Library, EMBASE, Medline, Medline in process, PubMed and Web of Science, from 1st January 1996 to 29th June 2018. An updated Medline search was performed 30th June 2018 to 31st October 2019. Methods Randomised controlled trials (RCTs) and observational studies reporting health outcomes of infants and children born to women who received inactivated influenza vaccine during pregnancy. The primary outcome was infant laboratory confirmed influenza (LCI). Secondary outcomes included influenza-like illness (ILI), other respiratory illnesses, primary care, clinic visit or hospitalisations due to influenza illness and long-term respiratory childhood outcomes. Results 19 studies were included; 15 observational studies and 4 primary RCTs with an additional 3 papers reporting secondary outcomes of these RCTs. In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15–50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old. Two RCTs were excluded from the meta-analysis for the outcome of LCI in infants (different controls used). Both of these studies showed a protective effect for infants from LCI, with a vaccine efficacy of up to 70%. Overall observational studies showed an inverse (protective) association between maternal influenza vaccination and infant LCI, hospitalisation and clinic visits due to LCI or ILI in infants and other respiratory illness in infants ≤6 months old. Conclusions This systematic review supports maternal influenza vaccination as a strategy to reduce LCI and influenza-related hospitalisations in young infants. Communicating these benefits to pregnant women may support their decision to accept influenza vaccination in pregnancy and increase vaccine coverage in pregnant women. Registration PROSPERO CRD42018102776.

School-based vaccination (SBV) and checking students’ vaccination records at school have the potential to optimize vaccination coverage among school-aged children. The primary aim of this paper is to describe adoption of SBV by countries from 2008 to 2017, including target age groups and vaccines delivered in 2017, as reported annually through the World Health Organization (WHO)-United Nations Children’s fund (UNICEF) Joint Reporting Form (JRF). Expanding upon previous analyses, country-specific rates of primary school enrollment and home-based record (HBR) ownership were linked to the WHO-UNICEF JRF data, to identify countries with high potential to implement vaccination record checks at school. The proportion of countries reporting delivery of at least one routinely recommended vaccine dose in school settings increased from 95 (of 163 reporting; 58%) in 2008 to 108 (of 181 reporting; 60%) in 2017. The 13 additional countries that reported using SBV in 2017 were among 31 countries for which SBV data from the JRF were unavailable in 2017. The most common antigens delivered through SBV in 2017 were tetanus (94 countries), diphtheria (89 countries), and human papillomavirus (52 countries). Among 93 countries with data available for net primary school enrollment and HBR ownership, 52 (56%) countries had both ≥80% net primary school enrollment and ≥80% of children aged 12–23 months ever owning an HBR; 33 (63%) of these used SBV. If not already doing so, these 33 countries represent an opportunity to introduce routine checking of vaccination status at entry to, or during primary school. With the growing number of new vaccines and booster doses of childhood vaccines targeting school-age children, implementation of SBV and checking of student vaccination records at school may help improve vaccination coverage; however, additional data are needed to assess global prevalence of checking vaccination status at school and to identify factors facilitating optimal implementation of this strategy.

The coronavirus disease 2019 (COVID-19) vaccination drive in Pakistan began in February 2021 after half a million doses of Sinopharm vaccine (BBIBP-CorV vaccine) was supplied to the country by the People’s Liberation Army of China [1]. The National Command and Control Center (NCOC) managed the vaccination program in the country; the frontline healthcare workers were the first group to be vaccinated when the mass vaccination campaign began on February 3, 2021 [2]. Later, on February 22, 2021, the government initiated the vaccination campaign for other healthcare workers. On March 16, April 3, April 25, April 28, May 12, May 29, and June 3, 2021, a mass vaccination campaign was introduced for populations above the age of 70, 65, 60, 50, 40, 30, and 18, respectively [3]. While leading the national COVID-19 vaccination efforts in Pakistan, NCOC also drafted policies related to vaccines distribution to the provinces [3]. NCOC works closely with the provincial health departments and National Coordination Committee (NCC), headed by the Prime Minister of Pakistan. As of the last week of July 2021, the number of fully and partially vaccinated people in Pakistan has reached more than 6 million and 20 million, respectively (a total population of approximately 220 million). The total daily doses administered at designated COVID vaccination centers have increased to somewhere between 600,000 and 900,000 doses (as of the last week of July 2021), [3]. In this paper, we aimed to shed light on the dynamics of COVID-19 vaccination in Pakistan and discussed the potential solutions to the recognized problems.

Jordan is an upper-middle income country which was dramatically affected by two waves of COVID-19, the first wave in November 2020 and the second peaking mid-to-late March 2021. The country has developed its first National preparedness and response plan even before the first case of COVID-19 had been reported and has been being updating periodically. Similarly, Jordan has developed an effective plan for COVID-19 vaccine roll-out, thereby starting the registration to vaccination during late 2020. The aim of the vaccination program was changed from vaccinating 20% of the population to vaccinate over 5 million residents, corresponding to over 80% of the total population over the age of 18 years. Securing bilateral agreements and the ability to ensure additional vaccine supplies enabled the country to increase its vaccination target. Similar to equitable COVID-19 response in Jordan, COVID-19 vaccination plan includes all population, including refugees and migrants. 1.1. Strengthening existing immunization program The National Immunization Program (NIP) of Jordan is one of the most effective and successful public health programs which is highly trusted by the public. Country has reported immunization coverage rates over 90% for all vaccines during pre-COVID-19 period. A recent survey conducted by the World Bank reported that a country’s ability to roll out mass adult vaccination programs doesn’t depend on the existence of a well-functioning childhood immunization system [1]. This is evident through the recently established electronic registration, reporting, and monitoring system for COVID-19 vaccination. While childhood immunization is still relying on a paper-based vaccination electronic system, the COVID-19 vaccination data system is built on a solid electronic registration system, with minimal data entry.

A prenatal care provider's recommendation for maternal vaccines is one of the strongest predictors of vaccine acceptance during pregnancy. Aside from basic talking points, few resources exist to help obstetric care providers effectively navigate conversations with vaccine hesitant patients. This paper describes the development and acceptability of "VaxChat," an hour-long, evidence-based video tutorial aimed at improving obstetric care providers' ability to promote maternal vaccines. Between June and November 2017, 62 obstetric care providers registered to receive continuing medical education credit for viewing VaxChat. Of the post-tutorial responses received, over 90% said VaxChat increased their knowledge of what to say to vaccine hesitant patients, increased their confidence in addressing vaccinations with their pregnant patients, and will help them improve their practice culture regarding maternal vaccine promotion. Eighty percent intend to change how they approach vaccine conversations. These data suggest VaxChat may be a welcome complement to existing provider-to-patient talking points.

Background Streptococcus pneumoniae infection is associated with a high morbidity and mortality worldwide. There are currently >98 known serotypes; the most burdensome are covered by current pneumococcal conjugate vaccines (PCVs) such as PCV10 (Synflorix®) and (Prevnar 13®) PCV13. However, at present no PCV is available on the National Expanded Programme of Immunization (EPI) in Thailand. Methods Here we report a systematic review of studies regarding pneumococci associated with invasive pneumococcal disease (IPD) and non-IPD in Thailand. The NCBI PubMed database and Google Scholar were used to identify relevant papers published from 1st January 1990 to 21st August 2017. The quantitative analysis was reported as the distribution of serotypes across two age groups, ≤5 and >5 years old, as these were the most commonly reported. Where age was not stated, or data was combined, data were categorised as all ages. Results The search returned 15 relevant articles. From these the five most common disease-causing serotypes, in rank order, were 6B, 23F, 14, 19A and 19F. Vaccine coverage would be 55.3% for PCV10 and 69.7% for PCV13. There was insufficient data to draw conclusions regarding non-invasive disease-causing pneumococcal serotypes. Conclusion This review demonstrates that the serotypes which were most responsible for disease in Thailand are included in PCV10 and PCV13. Better surveillance data of IPD and non-IPD are required for monitoring vaccine effectiveness if PCV is implemented nationally.

The recent approval of multiple new vaccines and their introduction in many Gavi countries have been the impetus for efforts to reduce the costs of these vaccines. In this paper, we provide an overview of the main cost drivers for bringing second generation vaccines and compares these, where relevant, to the cost of bringing generic medicines to market. We argue that the main cost drivers for vaccine development are fixed, implying that second-generation vaccines do not lead to the same price reduction as normally seen with generic drugs. Lastly, we provide recommendations of the areas within vaccine development that could support further cost reductions.

Background Rotavirus is the leading cause of severe diarrhea among children worldwide, and vaccines can reduce morbidity and mortality by 50–98%. The test-negative control (TNC) study design is increasingly used for evaluating the effectiveness of vaccines against rotavirus and other vaccine-preventable diseases. In this study design, symptomatic patients who seek medical care are tested for the pathogen of interest. Those who test positive (negative) are classified as cases (controls). Methods We use a probability model to evaluate the bias of estimates of rotavirus vaccine effectiveness (VE) against rotavirus diarrhea resulting in hospitalization in the presence of possible confounding and selection biases due to differences in the propensity of seeking medical care (PSMC) between vaccinated and unvaccinated children. Results The TNC-based VE estimate corrects for confounding bias when the confounder’s effects on the probabilities of rotavirus and non-rotavirus related hospitalizations are equal. If this condition is not met, then the estimated VE may be substantially biased. The bias is more severe in low-income countries, where VE is known to be lower. Under our model, differences in PSMC between vaccinated and unvaccinated children do not result in selection bias when the TNC study design is used. Conclusions In practice, one can expect the association of PSMC (or other potential confounders) with the probabilities of rotavirus and non-rotavirus related hospitalization to be similar, in which case the confounding effects will only result in small bias in the VE estimate from TNC studies. The results of this work, along with those of our previous paper, confirm the TNC design can be expected to provide reliable estimates of rotavirus VE in both high- and low-income countries.

Vaccine coverage is routinely used as a performance indicator for immunization programs both at local and global levels. For many national immunization programs, there are challenges with accurately estimating vaccination coverage based on available data sources, however an increasing number of low- and middle-income countries (LMICs) have begun implementing electronic immunization registries to replace health facilities' paper-based tools and aggregate reporting systems. These systems allow for more efficient capture and use of routinely reported individual-level data that can be used to calculate dose-specific and cohort vaccination coverage, replacing the commonly used aggregate routine health information system data. With these individual-level data immunization programs have the opportunity to redefine performance measures to enhance programmatic decision-making at all levels of the health system. In this commentary, we discuss how measures for assessing vaccination status and program performance can be redefined and recalculated using these data when generated at the health facility level and the implications of the use and availability of electronic individual-level data.

Since its peak in early 2016, the incidence of Zika virus (ZIKV) cases has declined to such low levels that Phase 3 field efficacy trials may be infeasible. While great progress was made to rapidly advance several vaccine candidates into Phase 1 and 2 clinical trials, in the absence of sustained viral transmission it may be difficult to evaluate the effectiveness of ZIKV vaccine candidates by conducting traditional clinical disease endpoint efficacy studies. However, ZIKV is still circulating at low levels in some areas and is likely to re-emerge in naïve populations or in sites of prior epidemics once population immunity wanes. Therefore, the public health need for a ZIKV vaccine remains. To facilitate continued ZIKV vaccine development efforts, the World Health Organization's Initiative for Vaccine Research and the National Institutes of Health’s National Institute of Allergy and Infectious Diseases co-hosted a meeting of experts in March 2018 to identify strategies to demonstrate vaccine effectiveness in view of waning ZIKV disease incidence. This paper outlines points for consideration for developers, regulators, and other stakeholders working towards a licensed ZIKV vaccine. These deliberations may also be applicable to development of vaccines for other emerging infections where the size, unpredictability, and ephemeral nature of outbreaks makes clinical disease endpoint efficacy trials to demonstrate vaccine effectiveness infeasible.

Up until now, countries have adopted a 'isolate-test-treat-trace' strategy to contain the COVID-19 pandemic. The next critical intervention in the fight against COVID-19 will be effective delivery of safe and efficacious vaccines. Various countries such as the USA, the UK, Canada, Israel, etc., have started administering vaccines to priority population groups. India is gearing up its critical components of the vaccine delivery system to effectively deliver vaccines across the country and has prioritized certain population groups to whom the vaccine will be administered. Considering India's ambitious target to vaccinate close to 300 million people in the first phase of the vaccination drive with limited initial supply (which will be ramped up gradually), it is critical for stakeholders at all the levels - national, state and district - to understand the estimated need for vaccines across geographies based on the vulnerable population and disease epidemiology with the objective of preventing maximum number of future infections from the disease. This paper aims to describe a comprehensive geo-prioritization framework based on existing prevalence of COVID-19, high-risk co-morbidities, and demographic analysis to identify states/districts that could be most in need of the COVID-19 vaccines.

Background Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses. Methods An open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis. Results We enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns. Conclusion In patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients.

Replication-incompetent adenoviral vectors have been under investigation as a platform to carry a variety of transgenes, and express various antigens as a basis for preventive or therapeutic vaccine development. A replication incompetent adenoviral vector based on human adenovirus type 26 (Ad26) has been evaluated in several clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and features of recombinant viral vector vaccines. This paper reviews the biological features of the Ad26 vectors, including tabulation of safety and risk assessment characteristics of Ad26 vector-based vaccines. Substantial information on immunogenicity, clinical safety, biological characteristics and manufacturing are reported. In the Ad26 vector, deletion of the E1 gene, rendering the vector replication incompetent and providing space for transgene insertion, is combined with additional genetic engineering for vaccine manufacturability and transgene expression optimization. These vaccines are manufactured using the E1-complementing PER.C6® cell line, a continuous, human cell-line that can be cultured in serum-free medium in a suspension to high cell densities, providing an effective and flexible system for high-yield manufacturing. Ad26 vector vaccines have favorable thermostability profiles, compatible with vaccine supply chains. Safety data are compiled in the Ad26 vaccine safety database version 4.0, with unblinded data from 23 ongoing and completed clinical studies for a total of 3912 participants in Ebola, HIV, Malaria, RSV and Filovirus Ad26-based vaccine programs. Overall, all Ad26-based vaccines have been well tolerated, with no significant safety issues identified from the available data in the current Ad26 vaccine safety database. Evaluation of Ad26-based vaccines to further characterize the safety profile is continuing, with more than 90,000 participants vaccinated as of 1st July 2020 (cut-off date). Extensive evaluation of immunogenicity in humans shows strong and durable humoral and cellular immune responses. Clinical trials have not shown meaningful impact of pre-existing immunity to Ad26 on vaccine immunogenicity, even in the presence of Ad26 neutralizing antibody titers or Ad26-targeting T cell responses at baseline. The first vaccine, against Ebola virus, that makes use of the Ad26 vector, received marketing authorization from EC on 1st July 2020, as part of the Ad26.ZEBOV, MVA BN Filo vaccine regimen. New developments based on the Ad26 vector are underway, including a COVID-19 vaccine, which is currently in clinical evaluation.

Introduction Globally, knowledge of health workers has been documented to be key in effective immunisation service delivery. The parenteral route of drug administration is a vital healthcare procedure used in the administration of medicines using needle and syringe. Despite the importance of this procedure, improper handling of the device has resulted in an unsafe practice among health workers who attend to patients receiving injectable medications. A phased measles vaccination campaign (MVC) was conducted in 2017/2018 with a key objectives of training health workers on injection safety. This paper examines the association between improvement on knowledge of health workers through improved training curriculum and their practice on injection safety. Methods We reviewed information on handling and administration of the measles vaccine from the open data kit (ODK) platform finalised microplans and the training curriculum used during the 2015/2016 and 2017/2018 MVC. We analysed our results using paired t-test analysis, SPSS and Microsoft Excel spreadsheet and reported results in frequencies and proportions using charts and tables. Results Our findings revealed more health workers were trained during the 2017/2018 MVC as compared to 2015/2016 MVC. The curriculum adopted during the 2017/2018 MVC showed that multiple techniques were adopted during training compared to only class lectures used during the 2015/2016 MVC. A paired t-test analysis comparing the impact of training on the knowledge of the health workers during 2015/2016 and 2017/2018 MVC revealed significant improvement across five states during the 2017/2018 MVC, with mean ranging from 6.5% in the FCT to 23.7% in Nassarawa state. Conclusion The review of training curriculum and use of multiple training styles during the 2017/2018 MVC improved the knowledge of health workers. Immunisation programmes will benefit from adopting the training curriculum to meet the specific needs of the health workers.

Highlights • Process Flow Charts providing guidance on how to develop and licence a new veterinary vaccine. • The importance of producing a clear Target Product Profile (TPP) for a new veterinary vaccine. • What is required in order to move a new vaccine project from discovery through to development. • The differences between the human and veterinary vaccine development processes. • The commercial vaccine regulatory process leading to a marketing authorisation for a new product. • Identification of potential bottlenecks to the rapid development of a new veterinary vaccine., The UK Government recognised the importance of vaccines in the control of new emerging disease threats and in 2015 established the UK Vaccine Network to focus on specific areas of need. One of these was the understanding of what is involved in the development of a new vaccine and what are the potential bottlenecks to a rapid response in the face of an epidemic such as Ebola, MERS and more recently COVID-19. A Working Group was established to initially produce a Vaccine Development Process Map for a Human Vaccine. However, in view of the importance of animal wellbeing and the significant impact of diseases with Zoonotic potential, a similar Map has been created outlining the Veterinary Vaccine Development Process. This paper describes the production of that Map and covers the process from the generation of a Target Product Profile (TPP) through Discovery and Feasibility, and on to Product Development and Registration.

Background: Despite decent progress in Children Full Immunisation (CFI) in India during the last decade, surprisingly, Gujarat, an economically more developed state, had the second-lowest coverage of CFI (50%) in the country, lower than economically less developed states such as Bihar (62%). Further, the proportion of children with no immunisation in Gujarat has risen from 5% in 2005 to 9% in 2016. This paper investigated factors associated with the low level of CFI coverage in Gujarat.Methods: The study used two types of datasets: (1) the information on immunisation from 7730 children aged 12–23 months and their mothers from the fourth round of the Gujarat chapter of National Family Health Survey (NFHS 2015–16). (2) A macro (district) level data on both supply and demand-side factors of CFI are compiled from multiple sources. Bivariate and multivariate linear and logistic regression techniques were employed to identify the factors associated with CFI coverage.Results: In Gujarat, during 2015–2016, 50% of children aged 12–23 months did not receive full immunisation. The odds of receiving CFI was higher among children whose mothers had a Maternal and Child Protection (MCP) card (OR: 1.97, 95% CI 1.48–2.60) and those who received “high” maternal health services utilisation (OR: 1.59, 95% CI 1.10–2.26) compared to their counterparts. The odds of receiving CFI was about three times higher among the richest households (OR: 6.50, 95% CI 3.75–11.55) compared to their counterparts in the poorer households. Macro-level analyses suggest that poverty, maternal health care, and higher-order births are defining factors of CFI coverage in Gujarat.Conclusions: In order of importance, focusing on poverty, economic inequalities, pregnancy registration, and maternal health care services utilisation are likely to improve receiving CFI uptake in Gujarat. The disadvantageous position of urban areas and non-scheduled tribes in CFI coverage needs further investigation.

Launched at Davos in January 2017 with funding from sovereign investors and philanthropic institutions, the Coalition for Epidemic Preparedness Innovations (CEPI) is an innovative partnership between public, private, philanthropic, and civil organisations whose mission is to stimulate, finance and co-ordinate vaccine development against diseases with epidemic potential in cases where market incentives fail. As of December 2019, CEPI has committed to investing up to $706 million in vaccine development. This includes 19 vaccine candidates against its priority pathogens (Lassa fever virus, Middle East respiratory syndrome coronavirus, Nipah virus, Chikungunya, Rift Valley fever) and three vaccine platforms to develop vaccines against Disease X, a novel or unanticipated pathogen. As an entity largely supported by public funds, ensuring equitable access to vaccines whose development it supports in low- and middle-income countries is CEPI's primary focus. CEPI developed an initial equitable access policy shortly after its formation, with key stakeholders expressing strong views about its content and prescriptive nature. The CEPI board instructed that it be revisited after a year. This paper describes the process of revising the policy, and how key issues were resolved. CEPI will continue to take an iterative, rather than prescriptive, approach to its policy-one that reflects the needs of multiple stakeholders and ensures it can meet its equitable access goals.

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance systems accordingly. Targeted studies are needed, especially to better understand the effects of vaccinating seronegative individuals.

Background Vaccination is an effective way to prevent infectious diseases. Most studies analysed people's vaccine decisions, but few studies have analysed the effects of convenience such as immunisation schedule and distance and the quality of vaccination service on vaccination uptake. Objective The aim of this paper was to investigate adults’ preferences for convenience and quality of vaccination service, calculate the private economic benefit from convenience (vaccination schedule and distance) and quality, and predict the uptake rate for different vaccine scenarios. Methods In our study, we interviewed 266 adults in 2 counties of Shandong province in China. The discrete choice experiment (DCE) was employed to analyse the preference for hepatitis B virus (HBV) vaccination, and a mixed logit model was used to estimate respondent preferences for vaccination attributes included in the DCE. Results The protection rate against hepatitis B (HB), duration of protection, risk of side effects, vaccination cost, schedule, and vaccination sites were proved to influence adults’ preferences for HBV vaccination. The estimated willingness to pay (WTP) for 1 dose schedule instead of 3 doses and for a third-level vaccination site instead of a first-level site was almost equal (19 RMB). However, if the protection duration of the vaccination programme changed from 5 years to 20 years, the adults were willing to pay 35.05 RMB, and WTP for a 99% protection rate instead of a 79% rate was 67.71 RMB. The predicted uptake rate is almost 43% for the base case of HBV vaccination. Conclusions Adults made trade-offs between vaccination schedules, vaccination sites, and other characteristics of HBV vaccine. The impact of attributes of the vaccine itself, especially protection rate against HB, duration of protection, and risk of side-effects, is more dramatic than convenience and quality of vaccination service.

Nigeria is the most populous country in Africa and in 2012 was suffering some of the lowest vaccination rates in the World. A combination of factors had resulted in a dysfunctional immunization cold chain and supply chain. Recognizing that the number of unimmunized children contributed to high levels of under-5-mortality, and that health MDGs would not be attained, Minister of State for Health Mohammed Pate launched a vaccines transformation project in 2013. In partnership with BMGF, GAVI, UNICEF, WHO, other donors and implementing partners the transformation journey has so far taken three years and achieved impressive results. It has though faced challenges along the way and with the financial burden of GAVI graduation facing Nigeria, the economic downturn and the decentralized funding of health services, the results are far from sustained. This paper documents the work undertaken at the Federal level and then highlights specific work undertaken in partnership with Lagos State Government. It identifies the importance of taking an end to end approach and looking at the root causes of weak system performance. The strategy combined simple innovations in how data was captured, recorded and used to drive decision making. It included a comprehensive and systematic approach to cold chain procurement, installation and maintenance with a shift to a culture of active cold chain maintenance that is performing with higher levels of uptime. It also included supply chain redesign at both the Federal and State level. Finally, it involved an institutional transformation at the National Primary Health Care Development Agency (NPHCDA) to establish a data driven Department of Logistics and Health Commodities (DLHC) to manage the many challenges in immunizing 7.5 million children annually. While results have been impressive, there have been many challenges and lessons learned on the way. As Nigeria gets ready for its graduation from GAVI, a robust agile performing cold chain and supply chain will be essential for the good health of Nigeria's children and its economy. The necessary transformation journey has only just begun.

Background In the elderly, traditional influenza inactivated vaccines are often only modestly immunogenic, owing to immunosenescence. Given that adjuvantation is a means of enhancing the immune response, the trivalent inactivated vaccine adjuvanted with MF59 (MF59-TIV) was specifically designed to overcome this problem. Considering that, for ethical reasons, the absolute effectiveness of an influenza vaccine in the elderly cannot be demonstrated in placebo-controlled studies, the present study aimed to assess the effectiveness of MF59-TIV in preventing influenza-related outcomes in the elderly. Methods We conducted a systematic review of observational studies aimed at evaluating the effectiveness of MF59-TIV against influenza-related outcomes. Results of single studies were pooled whenever possible. Results Of the 1993 papers screened, 11 (6 case-control, 3 cohort and 2 prospective case-control) studies were identified. Hospitalization due to pneumonia/influenza and laboratory-confirmed influenza were reported in more than one study, while other outcomes (influenza-like illness, cardio- and cerebrovascular accidents) were investigated only by one study each. Pooled analysis of four case-control studies showed an adjusted MF59-TIV effectiveness of 51% (95% CI: 39–61%) against hospitalizations for pneumonia/influenza among community-dwelling seniors. Pooled results of the adjusted vaccine effectiveness against laboratory-confirmed influenza were also high (60.1%), although the 95% CI passed through zero (−1.3 to 84.3%). Other single community-based studies showed very high effectiveness of MF59-TIV in preventing hospitalizations for acute coronary [87% (95% CI: 35–97%)] and cerebrovascular [93% (95% CI: 52–99%)] events. MF59-TIV proved highly effective [94% (95% CI: 47–100%] in reducing influenza-like illness among institutionalized elderly. Furthermore, MF59-TIV displayed greater efficacy than non-adjuvanted vaccines in preventing hospitalizations due to pneumonia/influenza [adjusted risk ratio 0.75 (95% CI: 0.57–0.98)] and laboratory-confirmed influenza [adjusted odds ratio 0.37 (0.14–0.96)]. Conclusions Our results suggest that MF59-TIV is effective in reducing several influenza-related outcomes among the elderly, especially hospitalizations due to influenza-related complications.

Introduction The Global Polio Eradication Initiative (GPEI) massively invested to overcome the crippling disease in countries of the WHO African Region. In the context of economic crisis, almost all countries in the Region lack an adequate health workforce. Large amounts were invested by GPEI in human resources. This paper shows how the human resources funded by polio contributed to narrowing the gaps in health workforce and helped strengthening and supporting other priority health programmes in Angola, Chad, DRC, Nigeria, Tanzania, and Togo. Methods The health workforce strengthening methods used in the five different countries included the following: policy development and strategic planning, microplanning, capacity building of public health and community workers, implementation and services, monitoring and evaluation, advocacy and social mobilization, and programme review. Results Staff funded by polio helped with achieving good coverage in vitamin A and insecticide-treated mosquito nets (Angola, Chad); improvement of EPI and integrated disease surveillance indicators, improved quality of data (all five countries), administrative support, smooth introduction of new vaccines, increased case detection, and early isolation of patients suffering from the Guinea worm (Chad); reduction of cholera, extension of directly observed TB short course treatment (Democratic Republic of Congo); significant staff performance improvement (Nigeria). Discussion GPEI investment achieved far beyond its primary goal, and contributed to narrowing the gaps in the health workforce in countries of the African Region, as demonstrated by the best practice documentation exercise. We recommend that expertise and experience of polio funded staff should be leveraged to strengthen, expand and support other public health programmes.