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Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

2021; American Association for the Advancement of Science; Volume: 373; Issue: 6561 Linguagem: Inglês

10.1126/science.abj0299

1095-9203

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, Juan I. Moliva, 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, Renee van de Wetering, Seyhan Boyoglu-Barnum, Kwanyee Leung, Wei Shi, Eun Sung Yang, Yi Zhang, John-Paul Todd, Lingshu Wang, Gabriela Alvarado, 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, Mario Roederer, Nancy J. Sullivan, Daniel C. Douek, Barney S. Graham, Robert A. Seder,

COVID-19 Clinical Research Studies

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 μg 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.