Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.

2020-07-28

Corbett, Kizzmekia S., Barbara Flynn, Kathryn E. Foulds, Joseph R. Francica, Seyhan Boyoglu-Barnum, Anne P. Werner, Britta Flach, Sarah O’Connell, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Hanne Andersen, David R. Martinez, Amy T. Noe, Naomi Douek, Mitzi M. Donaldson, Nadesh N. Nji, Gabriela S. Alvarado, Darin K. Edwards, Dillon R. Flebbe, Evan Lamb, Nicole A. Doria-Rose, Bob C. Lin, Mark K. Louder, Sijy O’Dell, Stephen D. Schmidt, Emily Phung, Lauren A. Chang, Christina Yap, John-Paul M. Todd, Laurent Pessaint, Alex Van Ry, Shanai Browne, Jack Greenhouse, Tammy Putman-Taylor, Amanda Strasbaugh, Tracey-Ann Campbell, Anthony Cook, Alan Dodson, Katelyn Steingrebe, Wei Shi, Yi Zhang, Olubukola M. Abiona, Lingshu Wang, Amarendra Pegu, Eun Sung Yang, Kwanyee Leung, Tongqing Zhou, I. Ting Teng, Alicia Widge, Ingelise Gordon, Laura Novik, Rebecca A. Gillespie, Rebecca J. Loomis, Juan I. Moliva, Guillaume Stewart-Jones, Sunny Himansu, Wing-Pui Kong, Martha C. Nason, Kaitlyn M. Morabito, Tracy J. Ruckwardt, Julie E. Ledgerwood, Martin R. Gaudinski, Peter D. Kwong, John R. Mascola, Andrea Carfi, Mark G. Lewis, Ralph S. Baric, Adrian McDermott, Ian N. Moore, Nancy J. Sullivan, Mario Roederer, Robert A. Seder, and Barney S. Graham. 2020. "Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates." New England Journal of Medicine.

Background

Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.

Methods

Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.

Results

The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID₅₀) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.

Conclusions

Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

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