An optimized messenger RNA vaccine candidate protects non-human primates from Zika virus infection
Brooke Bollman, Naveen Nunna, Kapil Bahl, Chiaowen Joyce Hsiao, Hamilton Bennett, Scott Butler, Bryant M. Foreman, Katherine E. Burgomaster, Maya Aleshnick, Wing‐Pui Kong, Brian E. Fisher, Tracy J. Ruckwardt, Kaitlyn M. Morabito, Barney S. Graham, Kimberly A. Dowd, Theodore C. Pierson, Andrea Carfı́
Abstract
Zika virus (ZIKV), an arbovirus transmitted by mosquitoes, was identified as a cause of congenital disease during a major outbreak in the Americas in 2016. Vaccine design strategies relied on limited available isolate sequence information due to the rapid response necessary. The first-generation ZIKV mRNA vaccine, mRNA-1325, was initially generated and, as additional strain sequences became available, a second mRNA vaccine, mRNA-1893, was developed. Herein, we compared the immune responses following mRNA-1325 and mRNA-1893 vaccination and reported that mRNA-1893 generated comparable neutralizing antibody titers to mRNA-1325 at 1/20th of the dose and provided complete protection from ZIKV challenge in non-human primates. In-depth characterization of these vaccines indicated that the observed immunologic differences could be attributed to a single amino acid residue difference that compromised mRNA-1325 virus-like particle formation.