Coronavirus vaccine development

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When the MERS CoV outbreak raised global health concerns, we initiated a program to develop a candidate vaccine. Based on prior studies to solve the spike structure of HKU1 (an endemic betacoronavirus) and finding stabilizing mutations that also stabilized MERS-CoV and SARS-CoV spike proteins, and prior research collaboration agreements with industry, we were able to respond quickly to the emergence SARS-CoV-2. When sequences were available we immediately ordered reagents to produce spike protein for structural studies, for the development of serological assays, and for probes to isolate B cells from survivors for antibody discovery. In collaboration with Moderna, we used information from our prior studies to develop a mRNA vaccine based on the stabilized spike structure of SARS-CoV-2. To characterize this vaccine we conducted in vivo studies in hamsters, mice and NHPs. Our recent work has focused on assessing the immune response following vaccination, understanding the impact of viral variants on immunization and attempting to define a correlate of protection. Immunization of hamsters, mice and NHPs with mRNA-1273 proved to be immunogenic and elicit a neutralizing humoral response. We showed it protects both upper and lower airway infection in mice and NHPs. We have also learned that mRNA-1273 elicited S-specific antibody levels correlated with the amount of viral replication in the upper and lower airway following SARS-CoV-2 challenge in NHPs. Furthermore, our studies have shown that the number of immunizations impacts protection and that a two-dose mRNA-1273 vaccine regimen protects NHPs from beta infection. This work has validated the prototype pathogen approach to pandemic preparedness that we have advocated as a proactive method that would systematically establish the reagents and knowledge base needed to address all 25 virus families known to infect humans. The steps taken to make this unprecedented response to a new viral pandemic threat will serve as a template for responses to future emerging viruses.