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, 22 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 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.

Vaccine Preparedness for the Next Influenza Pandemic: A Regulatory Perspective.

The response to SARS-CoV-2 demonstrated the tremendous potential of investments in vaccine research and development to impact a global pandemic, resulting in the rapid development and deployment of lifesaving vaccines. However, this unprecedented speed was insufficient to either effectively combat initial waves of the pandemic or adapt in real time to new variants. This review focuses on opportunities from a public health oriented regulatory perspective for enhancing research, development, evaluation, production, and monitoring of safety and effectiveness to facilitate more rapid availability of pandemic influenza vaccines. We briefly review regulatory pathways and processes relevant to pandemic influenza, including how they can be strengthened and globally coordinated. We then focus on what we believe are critical opportunities to provide better approaches, tools, and methods to accelerate and improve vaccine development and evaluation and thus greatly enhance pandemic preparedness. In particular, for the improved vaccines needed to respond to a future influenza pandemic better and more rapidly, moving as much of the development and evaluation process as possible into the pre-pandemic period is critical, including through approval and use of analogous seasonal influenza vaccines with defined immune correlates of protection.

The Regulatory Evaluation of Vaccines for Human Use.

A vaccine is an immunogen, the administration of which is intended to stimulate the immune system to prevent, ameliorate, or treat a disease or infection. A vaccine may be a live attenuated preparation of microorganisms, inactivated (killed) whole organisms, living irradiated cells, crude fractions, or purified immunogens, including those derived from recombinant DNA in a host cell, conjugates formed by covalent linkage of components, synthetic antigens, polynucleotides (such as the plasmid DNA vaccines), mRNA, living vectored cells expressing specific heterologous immunogens, or cells pulsed with immunogen. Vaccines are highly complex products that differ from small molecule drugs because of the biological nature of the source materials such as those derived from microorganisms as well as the various cell substrates from which some are derived. Regardless of the technology used, because of their complexities, vaccines must undergo extensive testing and characterization. Special expertise and procedures are required for the manufacture, control, and regulation of vaccines. Throughout their life cycle from preclinical evaluation to post-licensure lot release testing, vaccines are subject to rigorous testing and oversight by manufacturers and national regulatory authorities. In this chapter, an overview of the regulatory evaluation and testing requirements for vaccines is presented.

Human Challenge Studies for Vaccine Development : Regulatory Aspects of Human Challenge Studies.

The traditional regulatory pathway for the evaluation of new vaccine candidates generally proceeds from preclinical through three successive phases of human trials, and the demonstration of efficacy is usually done through randomized-controlled clinical trials. However, human challenge trials or controlled human infection models have been used in vaccine clinical development to generate supportive data for establishment of correlates of protection, supportive data for licensure, as well as licensure in the case of Vaxchora® by the US FDA. Despite this, there are no codified regulations from national regulatory authorities (NRAs) that specifically address HCTs, nor guidance related to standardization of approaches to HCTs among regulators. NRAs may agree that HCTs are innovative, promising tools to accelerate vaccine development; however, a strong benefit/risk assessment is needed to ensure the safety of study participants. Lastly, it is important to consider the regulatory framework in which the human challenge trial may be conducted.