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[Preprint]. 2021 Apr 23:2021.04.20.440647. [Version 2] doi: 10.1101/2021.04.20.440647

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 Montefiori, Mehul S Suthar, Adrian McDermott, Nancy J Sullivan, Mario Roederer, Daniel C Douek, Barney S Graham, Robert A Seder
PMCID: PMC8077626  PMID: 33907752

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.

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The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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