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

2021; Cold Spring Harbor Laboratory; Linguagem: Inglês

10.1101/2021.04.20.440647

Kizzmekia S. Corbett, Martha Nason, Britta Flach, Matthew Gagné, Sarah O’ Connell, Timothy S. Johnston, Shruti Shah, Venkata Viswanadh Edara, Katharine Floyd, Lilin Lai, Charlene McDanal, Joseph R. Francica, Barbara J. Flynn, Kaichun Wu, Angela Choi, Matthew Koch, Olubukola M. Abiona, Anne P. Werner, Gabriela Alvarado, Shayne F. Andrew, Mitzi M. Donaldson, Jonathan Fintzi, Dillon R. Flebbe, Evan Lamb, Amy T. Noe, Saule 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, Hanné Andersen, Kathryn E. Foulds, Darin K. Edwards, John R. Mascola, Ian N. Moore, Mark G. Lewis, Andrea Carfı́, David C. Montefiori, Mehul S. Suthar, Adrian B. McDermott, Nancy J. Sullivan, Mario Roederer, Daniel C. Douek, Barney S. Graham, Robert A. Seder,

COVID-19 Clinical Research Studies

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.