Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
Kizzmekia S Corbett, 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, Barney S Graham, Kizzmekia S Corbett, 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, Barney S Graham
Abstract
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.).
Copyright © 2020 Massachusetts Medical Society.
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