Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates
Kizzmekia S. Corbett,
Kathryn E. Foulds,
Saule T. Nurmukhambetova,
Kevin W. Bock,
Bianca M. Nagata,
Alex Van Ry,
Timothy S. Johnston,
Elham Bayat Mokhtari,
Amy R Henry,
Gabriela S. Alvarado,
Darin K Edwards,
Mark G. Lewis,
Mehul S Suthar,
Martha C. Nason,
Nancy J. Sullivan,
Daniel C. Douek,
Barney S Graham,
Robert A. Seder
Posted 24 May 2021
bioRxiv DOI: 10.1101/2021.05.21.445189
Posted 24 May 2021
Background: Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351. Methods: Nonhuman primates received 30 or 100 microgram of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 microgram at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge. Results: Eight weeks post-boost, 100 microgram x2 of mRNA-1273 induced reciprocal ID50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 microgram x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 microgram. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 microgram x2 of mRNA-1273, and there was a ~2-log reduction in sgRNA in NHP that received two doses of 30 microgram compared to controls. In nasal swabs, there was a 1-log10 reduction observed in the 100 microgram x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge. Conclusions: Immunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.
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