Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
Creators: name: Douek, N. 
name: Graham, B.S.
name: Wang, L. 
name: Edwards, D.K. 
name: Donaldson, M.M. 
name: Gordon, I. 
name: Noe, A.T. 
name: Steingrebe, K. 
name: Putman‑Taylor, T. 
name: Flebbe, D.R. 
name: Lin, B.C. 
name: Mascola, J.R. 
name: Doria‑Rose, N.A. 
name: Flynn, B.
name: Martinez, D.R.  
name: Abiona, O.M. 
name: Phung, E. 
name: Chang, L.A. 
name: Nason, M.C. 
name: Van Ry, A.
name: Kong, W.‑P. 
name: Pegu, A. 
name: O'Connell, S. 
name: Zhang, Y.  
name: Corbett, K. S.
name: Himansu, S.
name: Campbell, T.‑A. 
name: Yap, C. 
name: Teng, I‑T. 
name: Sullivan, N.J. 
name: Moore, I.N. 
name: Alvarado, G.S. 
name: Werner, A.P.
name: Schmidt, S.D. 
name: Greenhouse, J. 
name: Ruckwardt, T.J. 
name: McDermott, A. 
name: Lewis, M.G. 
name: Dodson, A. 
name: Nji, N.N. 
name: Moliva, J.I. 
name: Minai, M. 
name: Widge, A. 
name: Lamb, E. 
name: Gaudinski, M.R. 
name: Stewart‑Jones, G. 
name: Flach, B. 
name: Bock, K.W. 
name: Baric, R.S.
name: Morabito, K.M. 
name: Loomis, R.J.
name: Louder, M.K. 
name: Andersen, H. 
name: O'Dell, S.
name: Gillespie, R.A. 
name: Shi, W. 
name: Francica, S.
name: Ledgerwood, J.E. 
name: Seder, R.A.
name: Leung, K. 
name: Todd, J.‑P.M. 
name: Boyoglu‑Barnum, S.
name: Roederer, M.
name: Nagata, B.M. 
name: Novik, L.
name: Zhou, T.
name: Carfi, A. 
name: Pessaint, L. 
name: Cook, A. 
name: Yang, E.S. 
name: Strasbaugh, A. 
name: Foulds, K.
name: Browne, S. 
name: Kwong, P.D. 
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2020

description: 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.).