A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.

Vaccination barriers and drivers in Romania: a focused ethnographic study.

BACKGROUND: In 2016-18, a large measles outbreak occurred in Romania identified by pockets of sub-optimally vaccinated population groups in the country. The aim of the current study was to gain insight into barriers and drivers from the experience of measles vaccination from the perspectives of caregivers and their providers. METHODS: Data were collected by non-participant observation of vaccination consultations and individual interviews with health workers and caregivers in eight Romanian clinics with high or low measles vaccination uptake. Romanian stakeholders were involved in all steps of the study. The findings of this study were discussed during a workshop with key stakeholders. RESULTS: Over 400 h of observation and 161 interviews were conducted. A clear difference was found between clinics with high and low measles vaccination uptake which indicates that being aware of and following recommended practices for both vaccination service delivery and conveying vaccine recommendations to caregivers may have an impact on vaccine uptake. Barriers identified were related to shortcomings in following recommended practices for vaccination consultations by health workers (e.g. correctly assessing contraindications or providing enough information to allow an informed decision). These observations were largely confirmed in interviews with caregivers and revealed significant knowledge gaps. CONCLUSIONS: The identification of key barriers provided an opportunity to design specific interventions to improve vaccination service delivery (e.g. mobile vaccination clinics, use of an electronic vaccination registry system for scheduling of appointments) and build capacity among health workers (e.g. guidance and supporting materials and training programmes).

A Research and Development (R&D) roadmap for influenza vaccines: Looking toward the future.

Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza vaccine R&D. The roadmap covers a 10-year timeframe and is organized into six sections: virology; immunology; vaccinology for seasonal influenza vaccines; vaccinology for universal influenza vaccines; animal and human influenza virus infection models; and policy, finance, and regulation. Each section identifies barriers, gaps, strategic goals, milestones, and additional R&D priorities germane to that area. The roadmap includes 113 specific R&D milestones, 37 of which have been designated high priority by the IVR expert taskforce. This report summarizes the major issues and priority areas of research outlined in the IVR. By identifying the key issues and steps to address them, the roadmap not only encourages research aimed at new solutions, but also provides guidance on the use of innovative tools to drive breakthroughs in influenza vaccine R&D.

Social media strategies to affect vaccine acceptance: a systematic literature review.

Introduction: Vaccine hesitancy, defined as a delay in the acceptance or the refusal of vaccines despite their availability, is a growing global threat. More individuals are turning to social media for health information, including vaccine information. As such, there is an opportunity to leverage online platforms as a means to disseminate and persuade individuals toward vaccine acceptance. We sought to review literature focused on the influence of exposure to social media content on vaccine acceptance or hesitancy.Areas covered: This review focused on social networking sites (e.g. Facebook) and content communities (e.g. YouTube), to understand how exposure to vaccine information affected vaccine knowledge, attitudes, and intentions/behaviors. We searched PubMed, CINAHL, Scopus, and Inspec. We included English-language materials published from 2004 to 2020 and included interventional studies, observational studies, and impacts of policies. We excluded systematic reviews, protocols, editorials, letters, case reports, case studies, commentaries, opinion pieces, narrative reviews, and clinical guidelines.Expert opinion: Social media interventions to affect vaccine acceptance is a new but growing area of study. How a communication message is framed, who delivers the message, and network structure are critical for affecting the vaccine decision-making process. Social media should be leveraged to impact vaccine uptake.

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response.

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely - and at times uniquely - affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group - a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy - in consultation with a variety of external experts and stakeholders.

The Coalition Against Typhoid: Mobilizing a Community for a Global Fight.

Typhoid became a low priority on the global public health agenda when it was largely eliminated from developed countries in the 1940s. However, communities in South Asia and sub-Saharan Africa continue to bear the brunt of the disease burden. One strategy to increase attention and coordinate action is the creation of a coalition to act as a steward for typhoid. The Coalition against Typhoid (CaT) was created in 2010 with the mission of preventing typhoid among vulnerable populations through research, education, and advocacy. CaT successfully raised the profile of typhoid through convening the community with a biennial international conference that has experienced growing participation, disseminating data and news through a website and newsletter with increasing readership, and advocating through social media and a blog reaching a diverse audience. In 2017, CaT joined forces with the Typhoid Vaccine Acceleration Consortium to "Take on Typhoid," combining advocacy and communications efforts to mobilize researchers, clinicians, and decision makers at the global, regional, and local levels to introduce the new typhoid conjugate vaccine. As a result, the knowledge base, political will, and momentum are increasingly in place to implement prevention and control interventions including the typhoid conjugate vaccine in the poor communities that have historically been left behind.

Strengthening legal frameworks for vaccination: The experiences of Armenia, Georgia, and Moldova.

BACKGROUND: Gavi, the Vaccine Alliance, delivers life-saving vaccines to children in the world's poorest countries and encourages countries to assume increasing ownership of their immunization programs as their economies grow. Vaccination legislation may promote country ownership and immunization program sustainability. However, despite establishment of vaccination laws as an indicator of national commitment to immunization through the Global Vaccine Action Plan, little is known about the content of vaccination legislation in low- and middle-income countries and the processes by which countries strengthen their legal frameworks. We describe the experiences of three countries supported by Gavi through its partnership with the Sabin Vaccine Institute- Armenia, Georgia, and Moldova-in strengthening their legal frameworks for vaccination as they transition from Gavi support. METHODS: Information presented comes from national legal documents and the 2017 European Regional Workshop on Immunization Legislation, in which legislators and health officials from Armenia, Georgia, and Moldova shared approaches to making immunization a national priority by strengthening legal frameworks. We outline each country's legislative framework, describe progress in modifying vaccination legislation, and present strategies developed by countries to continue strengthening the legal basis of their immunization programs. RESULTS: Armenia, Georgia, and Moldova have legal frameworks that guarantee immunization as a public good, define immunization calendars, and establish regulations for vaccine procurement and administration. Legislative priorities include modifications of regulations to optimize procurement (Armenia and Moldova), potential provisions to increase vaccination through incentives (Georgia) or requirements (Moldova, possibly Armenia), and new mechanisms to finance routine program costs (all three countries). Each country is employing a distinct approach to strengthen its legal framework. CONCLUSION: These country experiences suggest that while legal approaches can promote country ownership, there is no standardized approach to vaccination legislation. A better understanding of the complex legal frameworks and their impact on supporting and sustaining progress in vaccination is needed.

Typhoid conjugate vaccines: a new tool in the fight against antimicrobial resistance.

Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines.

The National Vaccine Advisory Committee at 30: Impact and opportunity.

Thirty years after passage of legislation that created the National Vaccine Advisory Committee (NVAC) "to achieve optimal prevention of human infectious diseases through immunization and to achieve optimal prevention against adverse reactions to vaccines," this review reflects NVAC's role and impact on the U.S. vaccine and immunization enterprise as an external advisor to the Department of Health and Human Services. We reviewed the history of NVAC in the context of the principles of its establishment, with a focus on its reports and recommendations. We performed a systematic literature review to identify NVAC reports published in widely-accessible public health journals, and we reviewed the available archives to identify other reports and resolutions approved by the committee not published in journals. We characterized key issues considered by NVAC according to the five goals of the 2010 National Vaccine Plan. The predominance of NVAC activities to date related to the implementation of immunization across the lifespan and the many aspects of the system needed to foster the goal of full immunization. Reflecting on the impacts of NVAC to date, this review identified 30 NVAC approved reports published in journals, 22 stand-alone resolutions, and 26 unique unpublished reports. The development of new and improved vaccines continues to represent a significant priority for NVAC, and we identified several challenges related to future vaccine innovation. Given the many factors that impact on policy changes in the vaccine and immunization enterprise, we encountered challenges associated with demonstrating attribution of specific policy changes to NVAC recommendations. Although difficult to quantify, this review suggests that NVAC played an important role in the improvements in the U.S. immunization enterprise over the past 30 years and that NVAC can and will continue to play an important role supporting U.S. immunization going forward.

Beneficiary characteristics and vaccinations in the end-stage renal disease Medicare beneficiary population, an analysis of claims data 2006-2015.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) routinely recommends three vaccines - influenza, hepatitis B, and pneumococcal vaccines - for End-Stage Renal Disease (ESRD) dialysis patients. METHODS: We sought to assess vaccination coverage among fee-for-service (FFS) Medicare beneficiaries with ESRD who received Part B dialysis services at any point from January 1, 2006 through December 31, 2015 (through June 30, 2016 for influenza). To assess influenza vaccination rates in a given influenza season, we restricted the population to beneficiaries who were continuously enrolled in Medicare Parts A and B throughout all twelve months of that season. To assess hepatitis B and pneumococcal vaccine coverage following dialysis initiation, we developed a Kaplan-Meier curve for all patients who began dialysis between 2006 and 2015. RESULTS: For influenza vaccination, we identified an average of approximately 325,000 ESRD dialysis beneficiaries enrolled through each influenza season from 2006-2015. Seasonal influenza vaccination rates steadily increased during the 10-year period, from 52% in 2006-2007 to 71% in 2015-2016. The greatest increases in influenza vaccination appear in non-white beneficiaries with overall utilization in non-whites higher than in whites (p < .001). For the hepatitis B and pneumococcal vaccinations, we identified over 350,000 ESRD dialysis beneficiaries who began dialysis over the 10-year study window. The probability of receiving a hepatitis B vaccine within the first three years of entering into the ESRD program was higher (77%) than the probability of receiving any pneumococcal vaccine (53%). 45% of ESRD patients completed at least one dose of the two hepatitis B series (three-dose or four-dose) at any time during the study period. CONCLUSIONS: Opportunities exist at regional and facility levels to improve vaccination coverage. Compliance to ACIP recommendations may directly affect risk for ESRD dialysis patients for complications from diseases that can be mitigated by vaccination.

Informing vaccine decision-making: A strategic multi-attribute ranking tool for vaccines-SMART Vaccines 2.0.

SMART Vaccines 2.0 software is being developed to support decision-making among multiple stakeholders in the process of prioritizing investments to optimize the outcomes of vaccine development and deployment. Vaccines and associated vaccination programs are one of the most successful and effective public health interventions to prevent communicable diseases and vaccine researchers are continually working towards expanding targets for communicable and non-communicable diseases through preventive and therapeutic modes. A growing body of evidence on emerging vaccine technologies, trends in disease burden, costs associated with vaccine development and deployment, and benefits derived from disease prevention through vaccination and a range of other factors can inform decision-making and investment in new and improved vaccines and targeted utilization of already existing vaccines. Recognizing that an array of inputs influences these decisions, the strategic multi-attribute ranking method for vaccines (SMART Vaccines 2.0) is in development as a web-based tool-modified from a U.S. Institute of Medicine Committee effort (IOM, 2015)-to highlight data needs and create transparency to facilitate dialogue and information-sharing among decision-makers and to optimize the investment of resources leading to improved health outcomes. Current development efforts of the SMART Vaccines 2.0 framework seek to generate a weighted recommendation on vaccine development or vaccination priorities based on population, disease, economic, and vaccine-specific data in combination with individual preference and weights of user-selected attributes incorporating valuations of health, economics, demographics, public concern, scientific and business, programmatic, and political considerations. Further development of the design and utility of the tool is being carried out by the National Vaccine Program Office of the Department of Health and Human Services and the Fogarty International Center of the National Institutes of Health. We aim to demonstrate the utility of SMART Vaccines 2.0 through the engagement of a community of relevant stakeholders and to identify a limited number of pilot projects to determine explicitly defined attribute preferences and the related data and model requirements that are responsive to user needs and able to improve the use of evidence for vaccine-related decision-making and consequential priorities of vaccination options.

Planning and priority setting for vaccine development and immunization.

We review a sequence of strategic planning efforts over time in the United States, all involving processes to prioritize new vaccine candidates. The Institute of Medicine of the National Academies of Sciences, Engineering, and Medicine has been involved in three priority setting processes, each using different metrics and methodologies: infant mortality equivalents (1985-1986), cost-effectiveness (2000), and more recently, the implementation of a software system based on a broader multi-criteria systems approach that can include either of the earlier metrics among other various considerations (2015). The systems approach offers users the flexibility to select, combine, rank, weigh and evaluate different attributes representing their perspectives, assumptions, and particular needs. This approach also overcomes concerns relating to the previous single-metric ranking approaches that yielded lists that, once published, were static, and could not readily accommodate new information about emerging pathogens, new scientific advances, or changes in the costs and performance features of interventions. We discuss the rationale and reasoning behind the design of this multi-criteria decision support approach, stakeholder feedback about the tool, and highlight the potential advantages from using this expanded approach to better inform and support vaccine policies.

Childhood immunizations: First-time expectant mothers' knowledge, beliefs, intentions, and behaviors.

INTRODUCTION: This study focused on how first-time mothers decide or intend to decide with respect to the recommended childhood immunization schedule. METHODS: This was the baseline survey of a larger longitudinal survey. Data were collected between June and September 2014 from 200 first-time mothers in their second trimester of pregnancy to examine vaccine-related knowledge, perceptions, intentions, and information-seeking behavior. RESULTS: Data were analyzed between January and June 2015. Seventy-five percent planned to have their child receive all the vaccinations consistent with the recommended childhood immunization schedule. Although participants expressed interest in childhood vaccine information, most had not received information directly from a primary care provider. One third reported receiving such information from their obstetrician/gynecologist but only about half of those were "very satisfied" with the information they received. About 70% indicated they were not familiar with the recommended vaccination schedule and number of routinely recommended vaccines. Familiarity with common vaccine education messages varied widely. Women who indicated they were planning to delay one or more recommended vaccinations were most likely to rely on Internet searches for childhood vaccine information. CONCLUSIONS: Overall, respondents had relatively positive beliefs and perceptions regarding childhood vaccines, which were associated with intentions to get their newborn vaccinated as recommended. However, most who were planning to delay recommended vaccinations or were undecided relied primarily on socially available sources of vaccine information, rather than information provided by a healthcare professional. Improved access to vaccine information from healthcare professionals could foster better vaccine-related knowledge and favorably impact vaccination decisions.

Childhood Immunizations: First-Time Expectant Mothers' Knowledge, Beliefs, Intentions, and Behaviors.

INTRODUCTION: This study focused on how first-time mothers decide or intend to decide with respect to the recommended childhood immunization schedule. METHODS: This was the baseline survey of a larger longitudinal survey. Data were collected between June and September 2014 from 200 first-time mothers in their second trimester of pregnancy to examine vaccine-related knowledge, perceptions, intentions, and information-seeking behavior. RESULTS: Data were analyzed between January and June 2015. Seventy-five percent planned to have their child receive all the vaccinations consistent with the recommended childhood immunization schedule. Although participants expressed interest in childhood vaccine information, most had not received information directly from a primary care provider. One third reported receiving such information from their obstetrician/gynecologist but only about half of those were "very satisfied" with the information they received. About 70% indicated they were not familiar with the recommended vaccination schedule and number of routinely recommended vaccines. Familiarity with common vaccine education messages varied widely. Women who indicated they were planning to delay one or more recommended vaccinations were most likely to rely on Internet searches for childhood vaccine information. CONCLUSIONS: Overall, respondents had relatively positive beliefs and perceptions regarding childhood vaccines, which were associated with intentions to get their newborn vaccinated as recommended. However, most who were planning to delay recommended vaccinations or were undecided relied primarily on socially available sources of vaccine information, rather than information provided by a healthcare professional. Improved access to vaccine information from healthcare professionals could foster better vaccine-related knowledge and favorably impact vaccination decisions.

Communicating the role and value of vaccine adjuvants.

Despite the inclusion of adjuvants in many routinely used vaccines to improve the immune response, their presence and role are neither clear in product details such as the packaging or in the Summaries of Product Characteristics, nor understood by health professionals or the public. For many vaccines the adjuvant may simply be described as 'Adsorbed' without clarification that the adsorbing onto a material such as aluminium hydroxide adjuvants the antigens. As many future vaccines are likely to be adjuvanted, the presence of adjuvants, either those used in existing vaccines or novel formulations, may raise public and professional concerns unless communication materials are prepared in advance to allay anxieties such as those that have arisen over some present vaccine ingredients such as thiomersal. This raises a dilemma about how active such communications should be: over-promotion of the presence of a new adjuvant may cause unneeded anxieties; under-promotion may raise concerns over concealment of information. Research is needed and appropriate communication materials should be prepared.