4.7 Article

mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates

Journal

NATURE IMMUNOLOGY
Volume 22, Issue 10, Pages 1306-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41590-021-01021-0

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Funding

  1. Intramural Research Program of the VRC
  2. NIAID
  3. NIH
  4. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority [75A50120C00034]
  5. Undergraduate Scholarship Program, Office of Intramural Training and Education, Office of the Director, NIH
  6. Emory Executive Vice President for Health Affairs Synergy Fund Award
  7. Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children's Healthcare of Atlanta, Woodruff Health Sciences Center 2020 COVID-19 CURE Award
  8. NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) [HHSN272201400004C]

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The mRNA-1273 vaccine from Moderna in a two-dose regimen provides strong protection against major variants of concern, particularly the B.1.351 variant. Higher neutralizing antibody responses and reduced viral replication in the upper and lower airways were observed after two doses, highlighting the importance of the full vaccine regimen for effective immunity.
B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 mu g of Moderna's mRNA-1273 vaccine, a single immunization of 30 mu g, or no vaccine. Two doses of 100 mu g of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was similar to 4- to 5-log(10) reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log(10) reduction in nasal swabs in the 100-mu g group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.

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