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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. publishedVersion

The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced following infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases (NIAID) within the National Institutes of Health (NIH) established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants potentially impacting transmission, virulence, and resistance to convalescent and vaccine-induced immunity. The SAVE program serves as a critical data-generating component of the United States Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines, and therapeutics and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity, and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models, and pivotal findings facilitated by this collaborative approach and identify future challenges. This program serves as a template for the response against rapidly evolving pandemic pathogens by monitoring viral evolution in the human population to identify variants that could erode the effectiveness of countermeasures.

Animal models that can recapitulate the human immune system are essential for the preclinical development of safe and efficacious vaccines. Development and optimization of representative animal models are key components of the NIAID strategic plan for the development of a universal influenza vaccine. To gain insight into the current landscape of animal model usage in influenza vaccine development, NIAID convened a workshop in Rockville, Maryland that brought together experts from academia, industry and government. Panelists discussed the benefits and limitations of the field's most widely-used animal models, identified currently available and critically needed resources and reagents, and suggested areas for improvement based on inadequacies of existing models. Although appropriately-selected animal models can be useful for evaluating safety, mechanism-of-action, and superiority over existing vaccines, workshop participants concluded that multiple animal models will likely be required to sufficiently test all aspects of a novel vaccine candidate. Refinements are necessary for all current model systems, for example, to better represent special human populations, and will be facilitated by the development and broader availability of new reagents. NIAID continues to support progress towards increasing the predictive value of animal models.

In response to global interest in the development of a universal influenza vaccine, the Bill & Melinda Gates Foundation, PATH, and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of experts (London, UK, May 2018) to assess the role of a standardized controlled human influenza virus infection model (CHIVIM) towards the development of novel influenza vaccine candidates. This report (in two parts) summarizes those discussions and offers consensus recommendations. Part 1 covers challenge virus selection, regulatory and ethical considerations, and issues concerning standardization, access, and capacity. This article (Part 2) summarizes the discussion and recommendations concerning CHIVIM methods. The panelists identified an overall need for increased standardization of CHIVIM trials, in order to produce comparable results that can support universal vaccine licensure. Areas of discussion included study participant selection and screening, route of exposure and dose, devices for administering challenge, rescue therapy, protection of participants and institutions, clinical outcome measures, and other considerations. The panelists agreed upon specific recommendations to improve the standardization and usefulness of the model for vaccine development. Experts agreed that a research network of institutions working with a standardized CHIVIM could contribute important data to support more rapid development and licensure of novel vaccines capable of providing long-lasting protection against seasonal and pandemic influenza strains.

A priority for the National Institute of Allergy and Infectious Diseases is development of a universal influenza vaccine providing durable protection against multiple influenza strains. NIAID will use this strategic plan as a foundation for future investments in influenza research.

In response to global interest in the development of a universal influenza vaccine, the Bill & Melinda Gates Foundation, PATH, and the Global Funders Consortium for Universal Influenza Vaccine Development convened a meeting of experts (London, UK, May 2018) to assess the role of a standardized controlled human influenza virus infection model (CHIVIM) towards the development of novel influenza vaccine candidates. This report (in two parts) summarizes those discussions and offers consensus recommendations. This article (Part 1) covers challenge virus selection, regulatory and ethical considerations, and issues concerning standardization, access, and capacity. Part 2 covers specific methodologic considerations. Current methods for influenza vaccine development and licensure require large costly field trials. The CHIVIM requires fewer subjects and the controlled setting allows for better understanding of influenza transmission and host immunogenicity. The CHIVIM can be used to identify immune predictors of disease for at-risk populations and to measure efficacy of potential vaccines for further development. Limitations to the CHIVIM include lack of standardization, limited access to challenge viruses and assays, lack of consensus regarding role of the CHIVIM in vaccine development pathway, and concerns regarding risk to study participants and community. To address these issues, the panel of experts recommended that WHO and other key stakeholders provide guidance on standardization, challenge virus selection, and risk management. A common repository of well-characterized challenge viruses, harmonized protocols, and standardized assays should be made available to researchers. A network of research institutions performing CHIVIM trials should be created, and more study sites are needed to increase capacity. Experts agreed that a research network of institutions working with a standardized CHIVIM could contribute important data to support more rapid development and licensure of novel vaccines capable of providing long-lasting protection against seasonal and pandemic influenza strains.