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 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 Carfi

doi:10.1038/s41541-023-00656-4

An optimized messenger RNA vaccine candidate protects non-human primates from Zika virus infection

NPJ Vaccines. 2023 Apr 20;8(1):58. doi: 10.1038/s41541-023-00656-4.

Authors

Brooke Bollman¹, Naveen Nunna², Kapil Bahl², Chiaowen Joyce Hsiao², Hamilton Bennett², Scott Butler³, Bryant Foreman⁴, Katherine E Burgomaster⁴, Maya Aleshnick⁴, Wing-Pui Kong⁵, Brian E Fisher⁵, Tracy J Ruckwardt⁵, Kaitlyn M Morabito⁵, Barney S Graham⁵, Kimberly A Dowd⁴, Theodore C Pierson⁴, Andrea Carfi²

Affiliations

¹ Moderna, Inc., Cambridge, MA, USA. [email protected].
² Moderna, Inc., Cambridge, MA, USA.
³ Takeda, Cambridge, MA, USA.
⁴ Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

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.