An optimized messenger RNA vaccine candidate protects non-human primates from Zika virus infection
Bollman, B. A.; Nunna, N.; Bahl, K.; Hsiao, C. J.; Bennett, H.; Butler, S.; Foreman, B.; Burgomaster, K. E.; Aleshnick, M.; Kong, W.-P.; Fisher, B. E.; Ruckward, T. J.; Morabito, K. M.; Graham, B. S.; Dowd, K. A.; Pierson, T.; Carfi, A.
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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.
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