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

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.

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.

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.

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

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

Highlights ► Mammalian review. ► Important veterinary viral immunodiseases. ► Immunoprophylaxis. ► Other control measures. ► Current status of vaccine research., This paper offers an overview of important veterinary viral diseases of mammals stemming from aberrant immune response. Diseases reviewed comprise those due to lentiviruses of equine infectious anaemia, visna/maedi and caprine arthritis encephalitis and feline immunodeficiency. Diseases caused by viruses of feline infectious peritonitis, feline leukaemia, canine distemper and aquatic counterparts, Aleutian disease and malignant catarrhal fever. We also consider prospects of immunoprophylaxis for the diseases and briefly other control measures. It should be realised that the outlook for effective vaccines for many of the diseases is remote. This paper describes the current status of vaccine research and the difficulties encountered during their development.

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.

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 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.

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.

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.

An orderly and effective vaccination campaign is essential in combating the global COVID-19 pandemic. As one of the pioneers, the U.S. Center for Disease Control proposes a phased plan to promote the vaccination process. This plan starts with vaccinating the high-priority population in Phase I, then turns to the remainder of the public in Phase II, and ends with a scale-back network in Phase III. The phased plan not only provides a sense of hope to impacted communities that this global pandemic can be defeated, but can serve as a template for other countries. To enhance this plan, this paper develops a generalizable framework for designing a hub-and-spoke vaccination dispensing network to achieve the goals in the Phase 2, which aims to expand the vaccination coverage for the general public. We introduce a new coverage index to measure the priority of different potential dispensing sites based on geo-data and develop an optimization model for network design. The hub-and-spoke network enhances the accessibility of the vaccines to various communities and helps to overcome the challenges related to ultra-cold storage facility shortage. A case study of Middlesex County in New Jersey is presented to demonstrate the application of the framework and provide insights for the Phase 2. Results from the baseline scenario show that increasing the driving time limit from 10 minutes to 25 minutes can improve the total coverage index from 40.8 to 55.9. Additionally, we explore how the changes of parameters impact the network design and discuss potential solutions for some special cases. When we allow 4 outreach nodes per hub, all potential 45 outreach points can be covered in the vaccination network within a 20-minute drive, and the total coverage index reaches its maximum value of 58.3.

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.

Human cytomegalovirus (HCMV) is currently a major cause of congenital disease in newborns and organ failure in transplant recipients. Despite decades of efforts, an effective vaccine against HCMV has yet to be developed. However, the discovery of pentameric gH complex on viral surface which contains potent neutralizing epitopes may help enable development of an effective vaccine. In our company ongoing Phase II clinical trial of whole-live virus HCMV vaccine (V160), the pentameric gH complex has been restored on the surface of live attenuated AD169 virus strain. The reconstructed HCMV virus contains a variety of surface glycoproteins including pentameric gH/gL/gUL128-131 complex, trimeric gH/gL/gO complex, gB glycoprotein, and gM/gN heterodimer complex. To further characterize this virus and enable the monitoring of multiple viral antigens during vaccine process development an effective and efficient analytical strategy was required to detect and quantify several viral surface proteins. In this paper, we present an innovative approach based on capillary western blot technology that allows fast and accurate quantitation of pentameric gH/gL/gUL128-131 complex, trimeric gH/gL/gO complex, and gB glycoprotein. This method is suitable for analyzing target proteins in multiple sample types including supernatants from infected cell culture, purification intermediates, concentration bulk, and the final vaccine product. In addition, the capillary western blot-based technology identified a previously unknown biochemical profile present in some HCMV viruses: triplet gH peaks of viral surface proteins in non-reducing environment, which could potentially present a new strategy for specificity and identity testing.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

It has been over twenty years since the first vaccines for the control of tick infestations became commercially available. These vaccines proved their efficacy and the potential of this approach for the control of tick-borne diseases (TBDs), which represent a growing burden for human and animal health worldwide. In all these years, research in this area has produced new tick-derived and pathogen-derived candidate protective antigens. However, the potential of vaccines for the control of TBDs has been underestimated due to major challenges to reduce tick infestations, pathogen infection, multiplication and transmission, tick attachment and feeding time and/or host pathogen infection. Nevertheless, vaccines constitute the most safe and effective intervention for the control of TBDs in humans, domestic and wild animals., Part of the research included in this paper was supported by the Ministerio de Economía, Industria y Competitividad (Spain) grant BFU2016-79892-P.

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.

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viral and other microbial pathogens in their genome (so-called "chimeric virus vaccines"). Many such viral vector vaccines are now at various stages of clinical evaluation. Here, we introduce an attenuated form of recombinant vesicular stomatitis virus (rVSV) as a potential chimeric virus vaccine for HIV-1, with implications for use as a vaccine vector for other pathogens. The rVSV/HIV-1 vaccine vector was attenuated by combining two major genome modifications. These modifications acted synergistically to greatly enhance vector attenuation and the resulting rVSV vector demonstrated safety in sensitive mouse and non-human primate neurovirulence models. This vector expressing HIV-1 gag protein has completed evaluation in two Phase I clinical trials. In one trial the rVSV/HIV-1 vector was administered in a homologous two-dose regimen, and in a second trial with pDNA in a heterologous prime boost regimen. No serious adverse events were reported nor was vector detected in blood, urine or saliva post vaccination in either trial. Gag specific immune responses were induced in both trials with highest frequency T cell responses detected in the prime boost regimen. The rVSV/HIV-1 vector also demonstrated safety in an ongoing Phase I trial in HIV-1 positive participants. Additionally, clinical trial material has been produced with the rVSV vector expressing HIV-1 env, and Phase I clinical evaluation will initiate in the beginning of 2016. In this paper, we use a standardized template describing key characteristics of the novel rVSV vaccine vectors, in comparison to wild type VSV. The template facilitates scientific discourse among key stakeholders by increasing transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.

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.

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.