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

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

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 (ID(50)) 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.)