Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates
By
Kizzmekia S. Corbett,
Martha C. Nason,
Britta Flach,
Matthew Gagne,
Sarah O'Connell,
Timothy S. Johnston,
Shruti N. Shah,
Venkata Vishwanadh 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 Todd,
Lingshu Wang,
Hanne Andersen,
Kathryn E. Foulds,
Darin K Edwards,
John R. K 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 Graham,
Robert A. Seder
Posted 21 Apr 2021
bioRxiv DOI: 10.1101/2021.04.20.440647
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 g 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 naive 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 SummarymRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.
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