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.

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.

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.

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.

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.

Addressing vaccine hesitancy: The potential value of commercial and social marketing principles and practices.

Many countries and communities are dealing with groups and growing numbers of individuals who are delaying or refusing recommended vaccinations for themselves or their children. This has created a need for immunization programs to find approaches and strategies to address vaccine hesitancy. An important source of useful approaches and strategies is found in the frameworks, practices, and principles used by commercial and social marketers, many of which have been used by immunization programs. This review examines how social and commercial marketing principles and practices can be used to help address vaccine hesitancy. It provides an introduction to key marketing and social marketing concepts, identifies some of the major challenges to applying commercial and social marketing approaches to immunization programs, illustrates how immunization advocates and programs can use marketing and social marketing approaches to address vaccine hesitancy, and identifies some of the lessons that commercial and non-immunization sectors have learned that may have relevance for immunization. While the use of commercial and social marketing practices and principles does not guarantee success, the evidence, lessons learned, and applications to date indicate that they have considerable value in fostering vaccine acceptance.

Translating vaccine policy into action: a report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings.

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life. In April 2012, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended revisions to the WHO position paper on influenza vaccines. For the first time, SAGE recommended pregnant women should be made the highest priority for inactivated seasonal influenza vaccination. However, the variable maternal influenza vaccination coverage in countries with pre-existing maternal influenza vaccine recommendations underscores the need to understand and to address the discrepancy between recommendations and implementation success. We present the outcome of a multi-stakeholder expert consultation on inactivated influenza vaccination in pregnancy. The creation and implementation of vaccine policies and regulations require substantial resources and capacity. As with all public health interventions, the existence of perceived and real risks of vaccination will necessitate effective and transparent risk communication. Potential risk allocation and sharing mechanisms should be addressed by governments, vaccine manufacturers, and other stakeholders. In resource-limited settings, vaccine-related issues concerning supply, formulation, regulation, evidence evaluation, distribution, cost-utility, and post-marketing safety surveillance need to be addressed. Lessons can be learned from the Maternal and Neonatal Tetanus Elimination Initiative as well as efforts to increase vaccine coverage among pregnant women during the 2009 influenza pandemic. We conclude with an analysis of data gaps and necessary activities to facilitate implementation of maternal influenza immunization programs in resource-limited settings.

Addressing parents' concerns: do multiple vaccines overwhelm or weaken the infant's immune system?

Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant's immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant's immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant's ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago.