As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks of unpredictable size and timing. This represents a major challenge in terms of both obtaining sufficient funding to develop vaccines, and the ability to evaluate clinical efficacy in the field. However, this also presents an opportunity in which vaccines, along with robust diagnostics and contact tracing, can be utilized to respond to outbreaks as they occur, and limit the potential for further spread of the disease in question. While mRNA-based vaccines have proven, during the COVID-19 response, to be an effective and safe solution in terms of providing a rapid response to vaccine development, virus vector-based vaccines represent a class of vaccines that can offer key advantages in certain performance characteristics with regard to viruses of pandemic potential. Here, we will discuss some of the key pros and cons of viral vector vaccines in the context of preparing for future pandemics.

Coronavirus disease 2019 (COVID-19) epidemiology and product landscapes have changed considerably since onset of the pandemic. Safe and effective vaccines and therapeutics are available, but the continual emergence of severe acute respiratory syndrome coronavirus 2 variants introduce limitations in our ability to prevent and treat disease. Project NextGen is a collaboration between the Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response, and the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, that is leveraging public–private partnerships to address gaps in the nation's COVID-19 vaccine and therapeutic capabilities. Targeted investments will advance promising next-generation candidates through the most difficult phases of clinical development to encourage further private sector interest for later stage development and commercial availability. New commercial vaccines and therapeutics that are more durable and effective across variants will improve our fight against COVID-19 and transform our response to future threats.

Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases. In many instances, vaccines may be needed in a reactive scenario, requiring technologies than can elicit rapid and robust immune responses with a single dose. Here, we discuss how viral vector vaccines are utilized in a vaccine portfolio for priority biological threats, some of the challenges in manufacturing viral vector vaccines, the need to strengthen live virus manufacturing capabilities, and future opportunities to capitalize on the use of viral vectors to improve the sustainability of the Biomedical Advanced Research and Development Authority’s vaccine portfolio.

Background: The advanced research, development, and regulatory approval of medical countermeasures (MCMs) for emerging pathogens remains critical to national health security. We created a conceptual framework to assess the feasibility of generating pivotal data to support FDA regulatory approval of vaccines and therapeutics against known pathogens. Our framework is intended to guide key portfolio decisions on developing MCMs for emerging viral pathogens. Methods: This framework draws on prior experience with MCM development programs, current FDA guidance, and insights from scientific, regulatory, and public health subject matter experts. We identified key requirements that impact the ability to generate pivotal data and assessed the likelihood of meeting these requirements based on current epidemiology, technical capabilities, and infrastructure. To demonstrate utility, we applied the framework to a subset of prioritized pathogens. Results: We identified eight factors central to assessing the feasibility of advanced development and FDA approval of vaccines and therapeutics. These factors were used to evaluate seven emerging pathogens to illustrate how the framework may inform investment decisions across disease contexts. Conclusions: This framework supports more efficient resource allocation by highlighting MCM candidates with the highest potential for FDA approval within existing regulatory paradigms. Given current conditions, vaccine development appears more feasible than therapeutics for the pathogens assessed, although regulatory pathways remain product- and context-specific. Close consultation with the FDA will be critical in defining appropriate regulatory strategies. This framework offers a structured, proactive approach to advance MCM development and strengthen national preparedness against emerging pathogens.