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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 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.

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. (C) 2019 Elsevier Ltd. All rights reserved. This research was funded by the University of Antwerp [BOF Concerted Research Action, Methusalem funding], NH acknowledges support from the chair in evidence-based vaccinology sponsored by a gift from Pfizer (2009-2018) and GSK (2016) and from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement 682540 - TransMID). This research was supported by the Antwerp Study Centre for Infectious Diseases (BID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors of Huijbers et al. [1] apologize for not giving sufficient credit to the work presented by Saupe et al. [2], Huijbers et al. [3] and Femel et al. [4]. Below are corrections to the relevant parts of the article. The authors would like to apologize for any inconvenience caused. Page 3054 (Introduction) The sentence: ‘In previous work we have shown that it is possible to break self-tolerance in mice, and to induce antibody responses against the tumor vascular markers extra domain A (EDA) and B (EDB) of the extracellular matrix molecule fibronectin.’, should be replaced by: ‘Previous work of Huijbers et al. [3] and Femel et al. [4] has shown that it is possible to break self-tolerance in mice, and to induce antibody responses against the tumor vascular markers extra domain A (EDA) and B (EDB) of the extracellular matrix molecule fibronectin.’ Page 3056 (Discussion) The sentence: ‘We have previously shown that the anti-self antibody response against EDB is decreased as the amount of TRX is increased.’, should be replaced by: ‘Saupe et al. [2] have previously shown that the anti-self antibody response against EDB is decreased as the amount of TRX is increased.’ Page 3057 (Discussion) The sentence: ‘In this paper we show that the TRX-part is absolutely required to induce an immune response against EDB and that vaccination with EDB alone does not induce an antibody response against EDB.’, should be replaced by: ‘In this paper Saupe et al. [2] show that the TRX-part is absolutely required to induce an immune response against EDB and that vaccination with EDB alone does not induce an antibody response against EDB.’ Page 3058 (Discussion) The sentence: ‘To address this issue, we have previously used the MMTV-PyMT transgenic model of breast cancer. Since EDB is not expressed in this model we approached the question with a vaccine against the extra domain A of fibronectin (EDA).’, should be replaced by: ‘This issue was previously addressed by Femel et al. [4] using the MMTV-PyMT transgenic model of breast cancer. Since EDB is not expressed in this model the question was approached with a vaccine against the extra domain A of fibronectin (EDA).’ The sentence: ‘We have looked into more detail at the immune response induced with the TRX-EDB vaccine [12] and found that the major subclass induced by the vaccine was IgG1, which is characteristic of a Th2-response, thus an antibody mediated immune response in mice. Furthermore, we found macrophages trying to engulf the tumor vessels in the tumors of mice vaccinated with TRX-EDB, increased fibrinogen leakage and increased neutrophil infiltration in these tumors.’, should be replaced by: ‘Huijbers et al. [3] have looked into more detail at the immune response induced with the TRX-EDB vaccine and found that the major subclass induced by the vaccine was IgG1, which is characteristic of a Th2-response, thus an antibody mediated immune response in mice. Furthermore, they found macrophages trying to engulf the tumor vessels in the tumors of mice vaccinated with TRX-EDB, increased fibrinogen leakage and increased neutrophil infiltration in these tumors.’ After the sentence: ‘The current study demonstrates that several alternative non-self fusion partners in conjugate vaccines can elicit strong and specific antibody responses against self-antigens.’, this sentence should be added: ‘This was also observed in a study by Saupe et al. in which VLRB (variable lymphocyte receptor B) conjugate vaccines were used [2]. This study concluded that the foreign antigen should be short (around 41 aa in size), have multimerizing capacity to provide a strong B cell activation signal and be hidden inside the vaccine protein to avoid epitope masking or clearance of the fusion protein.’ Page 3058 (Experimental procedures) The sentence: ‘The pET21-TRX vector was a kind gift of Dr. Anna-Karin Olsson (Uppsala University, Uppsala, Sweden).’, should be replaced by: ‘Both the pET21-TRX vector and the pET21a-TRX-EDB vector were a kind gift of Dr. Anna-Karin Olsson (Uppsala University, Uppsala, Sweden).’

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.

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.

Uncertainty surrounding the risk of developing and dying from Thrombosis and Thromobocytopenia 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 the existing evidence on the risks versus benefits of the AZ vaccine. We developed a Bayesian network to consolidate the existing 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 structure of the model, relevant variables, data to be included, 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 a 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 easily adaptable to international settings by re-parameterising it with local data. This paper provides detailed description of the model-building methodology, which can 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.

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 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.

Under the pandemic situation, there is an urgent need to produce and acquire sufficient quantities of prophylactic vaccines. It becomes important to devise a way to achieve reliable immunity with lower doses to distribute limited supplies of vaccines to maximum number of people very quickly. Intradermal (ID) vaccination is one such method to increase the effectiveness of vaccines. However, this method has not been widely used in general clinical practice because it is technically difficult to inject vaccines precisely into the ID tissue. Therefore, new ID delivery systems that allow reliable ID administration are under development. In this paper, we summarize its design and present the results of performance and usability testing for the Immucise™ Intradermal Injection System (Immucise™). This study showed that Immucise™ can reduce dead volume and inject drugs precisely into the ID tissues of subjects from infants to the elderly and can be used correctly and safely by healthcare professionals. This randomized controlled trial compared ID administration with Immucise™ and standard subcutaneous (SC) administration of seasonal influenza vaccine by analyzing the efficacy of the vaccine in the elderly group at 90 days and 180 days after administration. It was found that the vaccine for the ID group was as effective or more effective than that for the SC group up to 180 days later. It was also found that the geometric mean titer values, especially for B strains, were higher in the two-dose ID group than in the two-dose SC group. These findings suggest that Immucise™ is one of the best devices to distribute a small amount of vaccine quickly and widely to a larger number of people with little loss of vaccine during a pandemic.

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.

Sustainable demand for seasonal influenza vaccines is a component of national security strategies for pandemic preparedness. However, the ongoing COVID-19 pandemic has revealed many weaknesses in the capacity of countries to design and execute sustainable vaccination programs. An influenza pandemic remains a global threat and yet there is no global monitoring system for assessing progress towards influenza vaccination coverage targets. The International Federation of Pharmaceutical Manufacturers and Associations' (IFPMA) Influenza Vaccine Supply International Task Force (IVS) developed a survey method in 2008 to estimate seasonal influenza vaccination coverage rates, which in turn serves as a crude estimate of pandemic preparedness. It provides evidence to guide expanded efforts for pandemic preparedness, specifically for increasing COVID-19 vaccine immunization levels. Furthermore, the results presented herein serve as a proxy for assessing the state of pandemic preparedness at a global and regional level. This paper adds data from 2018 and 2019 to the previous analyses. The current data show an upward or stable global trend in seasonal influenza vaccine dose distributed per 1,000 population with a 7% increase between 2017 and 2018 and 6% increase between 2018 and 2019. However, considerable regional inequities in access to vaccine persist. Three regions, Africa, the Middle-east, and Southeast Asia together account for 50% of the global population but only 6% of distributed seasonal influenza vaccine doses. This is an important finding in the context of the ongoing COVID-19 pandemic, as distribution of influenza vaccine doses in many ways reflects access to COVID-19 vaccines. Moreover, improving seasonal vaccine uptake rates is critical for optimizing the annual benefits by reducing the huge annual influenza-associated societal burdens and by providing protection to vulnerable individuals against serious complications from seasonal influenza infections.

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

Older adults are at high risk from influenza and its complications, and are therefore an important population for prevention efforts. In Canada, public health efforts targeting influenza are multi-pronged and include vaccination programs as well as surveillance which informs the national surveillance reporting platform FluWatch run by the Public Health Agency of Canada. Recommendations regarding use of vaccines are made nationally by the National Advisory Committee on Immunization (NACI) and by the Comité sur l'immunisation du Québec in Quebec, while vaccination programs are planned and delivered at the provincial/territorial level as opposed to as a harmonized national immunization program. NACI performs rigorous targeted literature reviews to inform their statements, and recommendations also vary by whether they apply on Individual (pertaining to decisions for individual patients) vs. Programmatic (informing policy decisions for implementation of publicly funded vaccination programs) levels. This unique context results in inter-provincial variation in vaccine schedules and funded vaccine products. In this paper, the importance of influenza vaccination for older adults is discussed; to provide insights from the Canadian context, the evolution of NACI evidence reviews and recommendations on influenza vaccination is presented.

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.

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

International trends currently favour greater use of mandatory immunization. There has been little academic consideration or comparison of the existence and scope of mandatory immunization internationally. In this paper, we examine mandatory immunization in 28 Global NITAG (National Immunization Technical Advisory Group) Network (GNN) countries, including countries from every WHO region and World Bank income level classification. We found that although mandatory immunization programs, or mandatory elements within broader immunization programs, are relatively common, jurisdictions vary significantly with respect to the immunizations required, population groups affected, grounds for exemptions, and penalties for non-compliance. We also observed some loose associations with geography and income level. Based on these data, we categorized policies into a spectrum ranging from Narrow to Broad scope.

Highlights • Nigeria's immunization stakeholders cooperated on the 2016–17 MICS/NICS survey. • Extra survey clusters were added in 20 states to improve outcome precision. • Data from MICS & supplementary clusters were pooled after passing a statistical test. • Combined results were used to guide policy, but not as precise as originally hoped. • We explore organizational aspects of cooperation & technical aspects of pooled data., In 2015 immunization stakeholders in Nigeria were proceeding with plans that would have fielded two nationally representative surveys to estimate vaccination coverage at the same time. Rather than duplicate efforts and generate either conflicting or redundant results, the stakeholders collaborated to conduct a combined Multiple Indicator Cluster Survey (MICS) / National Immunization Coverage Survey (NICS) with MICS focusing on core sampling clusters and NICS adding supplementary clusters in 20 states, to improve precision of outcomes there. This paper describes the organizational and technical aspects of that collaboration, including details on design of the sample supplement and analysis of the pooled dataset. While complicated, the collaboration was successful; it yielded a unified set of relevant coverage estimates and fostered some novel sub-national results dissemination work.

Highlights • Nigeria’s national survey estimates of DPT3 and MCV1 coverage fluctuate greatly in recent years. • Much of the variation results from differences in surveys weights, not coverage. • Both USAID DHS and UNICEF MICS allow weights to vary from round-to-round. • Nigeria’s National Nutrition & Health Survey weights do not vary much due to post-stratification. • To compare results from surveys proximate in time, use similar strata weights for clarity., National vaccination coverage estimates from household surveys are widely used in monitoring and planning of immunization programs. In Nigeria, survey-reported national coverage estimates have shown large fluctuations in the past few years. In this paper, we examine the impact of state-level survey weighting on Nigeria’s national vaccination coverage estimation. In particular, we focus three vaccination-related outcomes among children aged 12–23 months: the coverage of the third dose of diphtheria, pertussis, and tetanus vaccine (DPT3); the coverage of the first dose of measles-containing vaccine (MCV1); and the availability rate of home-based vaccination record (HBR). We compare the sample selection and weight assignment of three major survey programs in Nigeria, and show that considerable portions of the changes in survey-reported national coverage estimates can be explained by shifts in state-level weights. Our analysis demonstrates the importance of state weighting method in estimating aggregated national coverage figures and provides important context for interpreting changes in coverage estimates between surveys in the future.

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.

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.

'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 peopleremain 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 tosynthesize recent literature on risk factors and interventions for zero- and missed-dosechildren 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.

Vaccine discovery and vaccination against preventable diseases are one of most important achievements of the human race. While medical, scientifictechnological advancements have kept in pace and found their way into treatment options for a vast majority of diseases, vaccines as a prevention tool in the public health realm are found languishing in the gap between such innovations and their easy availability/accessibility to vulnerable populations. This paradox has been best highlighted during the unprecedented crisis of the COVID-19 pandemic. As part of a two series publication on the vaccine industry's view on how to accelerate the availability of vaccines worldwide, this paper offers a deep dive into detailed proposals to enable this objective. These first-of-its-kind technical proposals gleaned from challenges and learnings from the COVID-19 pandemic are applicable to vaccines that are already on the market for routine pathogens as well as for production of new(er) vaccines for emerging pathogens with a public health threat potential. The technical proposals offer feasible and sustainable solutions in pivotal areas such as process validation, comparability, stability, post-approval changes, release testing, packaging, genetically modified organisms and variants, which are linked to manufacturing and quality control of vaccines. Ultimately these proposals aim to ease high regulatory complexity and heterogeneity surrounding the manufacturingdistribution of vaccines, by advocating the use of (1) Science and Risk based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. Capitalizingcollaborating on such new-world advancements into the science of vaccines will eventually benefit the world by turning vaccines into vaccination, ensuring the health of everyone.

Background In occurrence of the coronavirus disease 19 (COVID-19) pandemic, carrying out an efficient large-scale vaccination campaign is vital in order to control the virus. Especially in high prevalence areas of COVID – 19, it is crucial to implement an effective vaccination strategy. In Italy, programming an efficient COVID-19 mass vaccination campaign has been the main target of the Ministry of Health. Aims This paper gives a comprehensive overview of how the mass vaccination campaign is performed in Milan, one of the cities that has been mostly affected by the COVID-19 pandemic in Italy. We analyze the vaccination strategy implemented by Fondazione Ca’ Granda – Ospedale Maggiore Policlinico located in Milan. Furthermore, we compare the organization of this campaign in regards of those carried out across EU and UK. Materials and Methods The data derive from an analysis of the different vaccination plans implemented across EU and UK from the 27/12/2020 to the 15/06/2020. In addition, we discuss the data collected from the internal data server of IRCCS Fondazione Ca’ Granda – Ospedale Maggiore Policlinico from the 15/02/2021 to the 15/06/2021.The collected data are examined by means of descriptive statistics. Results From the analysis of the internal data server, we observe that the modular organization of Fiera Milano City guarantees up to 5000 vaccinations/day. Moreover, the precise flow organization of users and a series of strategies adopted to avoid identification errors or vaccine type administration errors are crucial to reach the aforementioned target. Conclusions The institution of mass vaccination centers thanks to the optimization of all the involved processes and the meticulous organization of these structures, allows to avoid crowds and guarantees the administration of elevated amounts of vaccines. All these elements assure a rapid vaccination coverage of the population in Lombardy, with a meaningful increase in daily administration doses.

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.

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.

Dear Editor, in their article, Garcia and Cerda [1] found a relatively high vaccine acceptance rate (90 6%) and stated that the COVID-19 pandemic has not only had a negative impact on people’s health and life behavior, but also on economies around the world Chi-squared and z-tests showed that the percentage of willing people is significantly higher amongst those who agree with the statement “I have the primary responsibility for preventing the infection by COVID-19” (63%) when compared with those who disagree (42 6%) [ ]our data showed that the percentage is higher amongst those people who agree that preventive behaviours are an act of social responsibility (64 1%), when compared to those who don’t agree (24 9%) In our opinion, developing a COVID-19 public vaccination program should start from considering people’s attitudes to engage them in an educational campaign focused on fostering the citizens-science alliance Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

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.

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.

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.

Highlights • LAIV has been used in Russia for decades. • Russian LAIV consistently provides superior effective protection against influenza. • It was incorporated into the WHO global pandemic influenza action plan. • A number of Russian LAIVs against pandemic influenza viruses have been prepared. • Russian LAIV technology was transferred to a number of developing countries., Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987. In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP. BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees. This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.

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.

Effective RI microplanning requires accurate population estimates and maps showing health facilities and locations of villages and target populations. Traditional microplanning relies on census figures to project target populations and on community estimates of distances, while GIS microplanning uses satellite imagery to estimate target populations and spatial analyses to estimate distances. This paper estimates the cost-effectiveness of geographical information systems (GIS)-based microplanning for routine immunization (RI) programming in two states in northern Nigeria. For our cost-effectiveness analysis, we captured the cost of all inputs for both approaches to capture the incremental cost of GIS over traditional microplanning and present the incremental cost-effectiveness ratios for each vaccine-preventable illness, death, and disability-adjusted life year (DALY) averted. We considered two scenarios for estimating vaccine requirements for each microplanning approach, one based on administrative vaccination coverage rates and one based on National Nutrition and Health Survey rates. With the administrative rates, GIS microplanning projected approximately 194,000 and 157,000 more required vaccinations than traditional microplanning in Bauchi and Sokoto States; with the survey rates, the additional number of vaccinations required was nearly 113,000 in Bauchi and about 47,000 in Sokoto. For each state under each scenario, we present numbers of and costs per measles and pertussis cases, deaths, and DALYs averted by the additional vaccinations, as well as annual costs. As expected, GIS-based microplanning incurs higher costs than traditional microplanning, due mainly to the additional vaccinations required for populations previously unreached. Our estimates of cost per DALY averted suggest, however, that GIS microplanning is more cost-effective than traditional microplanning in both states under both coverage scenarios and that the higher costs incurred by GIS microplanning are worth adopting.

Introduction It is important to quickly identify parent beliefs, intentions, and behaviors toward childhood vaccination, especially parents of children 19 to 35 months. This paper describes parental immunization beliefs, intentions, and behaviors; assesses the relationships between beliefs and intentions regarding child immunization and actual behaviors; and assesses whether beliefs, intentions, and/or behaviors varied across demographic subgroups. Methods A sample of parents, ages 18 and older, from a mobile panel with people residing in the U.S. were invited to answer immunization behavior, intention, and belief questions using a smartphone app that was not vaccine specific. 10,000 panel members with a child under 18 were sent invitations. 1029 surveys were completed by a respondent with a child 19 to 35 months. The survey instrument replicated many NIS questions and had similar sequencing. Findings Respondents reported that most children received all recommended vaccines, except flu vaccine, suggesting some may not understand the immunization schedule. Demographics closely associated with immunization behaviors were respondents’ education and household income. There is strong agreement that vaccines are effective, important to community health, and the child’s health. There is concern about the number of shots received, disease prevention, and ingredient safety. Some belief remains about vaccines causing learning disabilities. Positive beliefs about the benefits of childhood vaccines and concomitant risks vary with demographics. Conclusions This survey provided insights into beliefs and behaviors of parents regarding childhood vaccination. It found evidence of differences in beliefs, particularly related to delaying or declining recommended childhood vaccinations. The survey was conducted in a few days and at lower cost than traditional methods. This serves as a model for health agencies where rapid results or inexpensive approaches are needed.

Vaccination remains the most successful and effective mechanism of pathogen control. However, their development and deployment in epidemic settings have been limited, and the 2015 Ebola outbreak in West Africa identified several bottlenecks linked to a lack of investment in pathogen research, infrastructure or regulation. Shortly after this outbreak, the UK Government established the UK Vaccine Network to ensure the UK is better prepared to respond to pathogens outbreaks of epidemic potential. As part of their work, the network commissioned the creation of a Vaccine Development Tool (http://www.vaccinedevelopment.org.uk/) to serve as a guide to the key stages in vaccine development. The tool also set out to capture the key, rate-limiting bottlenecks in the development of vaccines against emerging infectious disease such that corrective action could be taken, be it through research, funding, infrastructure and policy, both in the UK and internationally. The main research bottlenecks were related to understanding pathogen biology, identification of appropriate animal models and investment in the manufacturing sciences, especially into process development. Infrastructure gaps in GMP manufacturing and fill-finish were also identified and limitations in GMO regulation and regulatory and ethical approvals, especially for outbreak pathogens required new policy initiatives. The UK Vaccine Network has since begun work to correct for these limitations with a series of funding calls and development programmes. This paper seeks to summarise the Vaccine Development Tool and its key findings.

As Australian First Nations people, public health practitioners and academics, we would like to thank Borg et al. for the raising the importance of increasing influenza vaccination rates [1]. The coverage of influenza immunisation in Australian First Nations children is close to 50% in the Northern Territory but is very low in most other states, thus this is a topic worthy of research. We would, however, like to offer an additional interpretation of their study results. Raising immunisation coverage from 4% to 6% is reported in the paper as a statistically significant result. We feel the most important result is that at least 94% of children remained unimmunised.