A safe and effective vaccine to protect against Zika virus infection is essential and should be feasible to develop, according to a commentary in the September 29th print issue of The New England Journal of Medicine by Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH); Hilary D. Marston, M.D., of NIAID; Nicole Lurie, M.D., M.S.P.H., Assistant Secretary for Preparedness and Response, U.S. Department of Health and Human Services; and Luciana L. Borio, M.D., acting chief scientist, U.S. Food and Drug Administration. The federal officials describe three potential strategies for conducting Zika vaccine clinical trials with each strategy dependent on disease incidence and likelihood of generating reliable data.
The authors discuss the challenges of vaccinating pregnant women and conclude that vaccinating women of childbearing age and their sexual partners is the optimal approach. If a Zika vaccine shows durable protection, vaccinating children could be an option in the future. Randomized controlled clinical trials are the preferred approach to Zika vaccine testing because of regional variations in Zika incidence and because any rare safety concerns would best be detected with such trials, according to the authors. With this in mind, three potential approaches to clinical trials are discussed. One is the traditional approach of Phase 1 and 2 clinical studies to assess a vaccine candidate’s safety and immunogenicity, including the impact of prior flavivirus exposure, followed by larger Phase 2b or 3 clinical studies examining specific aspects of efficacy, such as whether the vaccine protects against symptomatic infection alone.
A second strategy would be to conduct human challenge studies—trials in which individuals are vaccinated and then exposed to Zika virus under carefully controlled conditions—after a smaller Phase 1 vaccine study. This approach could be used if the epidemic subsides and disease incidence drops dramatically, making larger vaccine studies impractical. Careful ethical and safety review to weigh the risk to volunteers against potential public health benefit of a challenge trial is essential, the authors note. Challenge studies might identify immunological markers that could be used to support accelerated approval of Zika vaccine candidates. A third strategy could be to apply the “Animal Rule,” a regulatory pathway in which vaccine licensure would be based on data from trials in animals combined with sufficient safety and immunogenicity data from trials in humans. This approach would apply in situations where definitive human studies are not feasible, such as a dramatic drop in Zika incidence.
In all strategies communities affected by Zika infection must be actively engaged in clinical trial design and execution, the authors write.
HD Marston et al. Considerations for Developing a Zika Virus Vaccine. The New England Journal of Medicine DOI: 10.1056/NEJMp1607762 (2016).
NIAID Director Anthony S. Fauci, M.D.; Nicole Lurie, M.D., M.S.P.H., Assistant Secretary for Preparedness and Response, U.S. Department of Health and Human Services; and Luciana L. Borio, M.D., acting chief scientist, U.S. Food and Drug Administration are available for comment.