Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates

Kizzmekia S. Corbett; Martha C. Nason; Britta Flach; Matthew Gagne; Sarah O’Connell; Timothy S. Johnston; Shruti N. Shah; Venkata Viswanadh Edara; Katharine Floyd; Lilin Lai; Charlene McDanal; Joseph R. Francica; Barbara Flynn; Kai Wu; Angela Choi; Matthew Koch; Olubukola M. Abiona; Anne P. Werner; Gabriela S. Alvarado; Shayne F. Andrew; Mitzi M. Donaldson; Jonathan Fintzi; Dillon R. Flebbe; Evan Lamb; Amy T. Noe; Saule T. Nurmukhambetova; Samantha J. Provost; Anthony Cook; Alan Dodson; Andrew Faudree; Jack Greenhouse; Swagata Kar; Laurent Pessaint; Maciel Porto; Katelyn Steingrebe; Daniel Valentin; Serge Zouantcha; Kevin W. Bock; Mahnaz Minai; Bianca M. Nagata; Juan I. Moliva; Renee van de Wetering; Seyhan Boyoglu-Barnum; Kwanyee Leung; Wei Shi; Eun Sung Yang; Yi Zhang; John-Paul M. Todd; Lingshu Wang; Hanne Andersen; Kathryn E. Foulds; Darin K. Edwards; John R. Mascola; Ian N. Moore; Mark G. Lewis; Andrea Carfi; David Monterfiori; Mehul S. Suthar; Adrian McDermott; Nancy J. Sullivan; Mario Roederer; Daniel C. Douek; Barney S. Graham; Robert A. Seder

doi:10.1101/2021.04.20.440647

Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 – 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

One-Sentence Summary mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

Competing Interest Statement

K.S.C. and B.S.G. are inventors on U.S. Patent No. 10,960,070 B2 and International Patent Application No. WO/2018/081318 entitled Prefusion Coronavirus Spike Proteins and Their Use. K.S.C., O.M.A., and B.S.G. are inventors on US Patent Application No. 62/972,886 entitled 2019-nCoV Vaccine.