Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 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, Juan I. Moliva, Shayne F. AndrewMitzi 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, Renee van de Wetering, Seyhan Boyoglu-Barnum, Kwanyee Leung, Wei Shi, Eun Sung Yang, Yi Zhang, John Paul M. Todd, Lingshu Wang, Gabriela S. Alvarado, Hanne Andersen, Kathryn E. Foulds, Darin K. Edwards, John R. Mascola, Ian N. Moore, Mark G. Lewis, Andrea Carfi, David Montefiori, Mehul S. Suthar, Adrian McDermott, Mario Roederer, Nancy J. Sullivan, Daniel C. Douek, Barney S. Graham, Robert A. Seder

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167 Scopus citations

Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 mg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti-S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273-induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

Original languageEnglish
Article numbereabj0299
JournalScience
Volume373
Issue number6561
DOIs
StatePublished - 17 Sep 2021
Externally publishedYes

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