NIH Experts Detail Strategic Approach Needed for Development of a COVID-19 Vaccine

A harmonized and collaborative approach to coronavirus disease 2019 (COVID-19) vaccine research and development (R&D) is necessary for a successful outcome, according to a perspective published in Science. As COVID-19 vaccine development continues in the United States, different vaccine candidates have been presented by the government, industry, and academia for further trials.¹

However, the authors note that it is likely that more than 1 effective vaccine approach will be necessary to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19. Prevention of the virus will require a strategic approach to vaccine R&D that would allow essential data to be available for multiple vaccine candidates that are being tested in tandem.¹

The coauthors of the perspective are Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID); Francis Collins, MD, PhD, director of the National Institutes of Health (NIH); Lawrence Corey, MD, professor in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center in Seattle; and John R. Mascola, MD, director of NIAID's Vaccine Research Center.¹

The perspective also discusses the importance of defining efficacy for a COVID-19 vaccine. According the authors, the 2 most common endpoints for vaccine efficacy are¹:

• Protection from infection as defined by seroconversion, which is when an antibody has developed and become detectable in the blood
• Prevention of clinically symptomatic disease, especially amelioration of disease severity, including the frequency of disease requiring high-intensity medical care with some assessment of a decrease in hospitalization

Furthermore, these endpoints would require the close evaluation of COVID-19 vaccination in the context of different epidemiological and medical settings, among different age groups, and among underserved minorities.¹

The authors noted that immunization efforts have been moving swiftly using different vaccine platforms, such as traditional recombinant protein, replicating and nonreplicating viral vectors, and nucleic acid DNA and mRNA approaches. With each platform comes specific characteristics that provide advantages and limitations. Characteristics to consider include speed and flexibility of manufacture, safety and reactogenicity, the profile of humoral and cellular immunogenicity, durability of immunity, scale and cost of manufacturing, vaccine stability, and cold chain requirements. However, since a single vaccine or vaccine platform is unlikely to meet the global need, a strategic approach that supports testing multiple candidates that use different platforms will be critical.¹

In order to support discussion and consensus on vaccine trial designs, rapid data sharing, and collaborations between the public and private sectors, NIH partnered with its sister agencies in the Department of Health and Human Services, including the FDA, CDC, and Biomedical Advanced Research and Development Authority; other US government departments including the Departments of Defense and Veterans Affairs; the European Medicines Agency; and representatives from academia, philanthropic organizations, more than 15 biopharmaceutical companies, and the Foundation for NIH.¹

Within these COVID-19 Prevention Networks established under the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program, there is a growing consensus that vaccine trials should either use common independent laboratories or contribute samples and data that allow for the generation of surrogate markers that speed licensure of vaccine candidates, and an overall comparison of their efficacy, the authors note.²

Furthermore, the authors recommend the development of a common institutional review board and a common cross-trial data and safety monitoring board (DSMB) for the establishment of a regulatory framework that would be coordinated throughout the networks. These regulatory agencies would be able to work with the public to assess the efficacy of different approaches.¹

Although the focus for these networks and their regulatory agencies are primarily based in the United States, the COVID-19 Prevention Networks also have a global focus. Such a global collaboration will require coordination with the WHO, Coalition for Epidemic Preparedness Innovations, and other global philanthropic partners.¹

The authors also emphasize that manufacturing hundreds of millions to billions of doses of vaccines will require use of the vaccine-manufacturing capacity of the entire world. This means that, although new technologies and factories can be developed for production, immediate funding is necessary for biomanufacturing infrastructure that can meet the needs of global vaccine distribution.¹

Ultimately, all resources available in the public, private, and philanthropic sectors will need to collaborate strategically in order for the country to return to some semblance of previous normality, according to the authors. The ACTIV public-private partnership and collaborative harmonized efficacy trials are models that will allow this semblance of normality to occur.¹

REFERENCES

• Corey L, Mascola JR, Fauci AS, Collins FS. A strategic approach to COVID-19 vaccine R&D. Science. 2020. doi: 10.1126/science.abc5312.
• NIH experts: Coordinated strategy to accelerate COVID-19 vaccine candidates is key [news release]. NIH/National Institute of Allergy and Infectious Diseases; May 11, 2020. eurekalert.org/pub_releases/2020-05/nioa-nec051120.php. Accessed May 15, 2020.