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

Abstract

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 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg 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 ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg 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.

• Authors: Kizzmekia S Corbett, Anne P Werner, Sarah O' Connell, Matthew Gagne, Lilin Lai, Juan I Moliva, Barbara Flynn, Angela Choi, Matthew Koch, Kathryn E Foulds, Shayne F Andrew, Dillon R Flebbe, Evan Lamb, Saule T Nurmukhambetova, Samantha J Provost, Kevin W Bock, Mahnaz Minai, Bianca M Nagata, Alex Van Ry, Zackery Flinchbaugh, Timothy S Johnston, Elham Bayat Mokhtari, Prakriti Mudvari, Amy R Henry, Farida Laboune, Becky Chang, Maciel Porto, Jaclyn Wear, Gabriela S Alvarado, Seyhan Boyoglu-Barnum, John-Paul M Todd, Bridget Bart, Anthony Cook, Alan Dodson, Laurent Pessaint, Katelyn Steingrebe, Sayda Elbashir, Manjari Sriparna, Andrew Pekosz, Hanne Andersen, Kai Wu, Darin K Edwards, Swagata Kar, Mark G Lewis, Eli Boritz, Ian N Moore, Andrea Carfi, Mehul S Suthar, Adrian McDermott, Mario Roederer, Martha C Nason, Nancy J Sullivan, Daniel C Douek, Barney S Graham, Robert A Seder
• Journal: Nature immunology (Nat Immunol) Vol. 22 Issue 10 Pg. 1306-1315 (10 2021) ISSN: 1529-2916 [Electronic] United States
• PMID: 34417590 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines
• RNA, Viral
• Spike Glycoprotein, Coronavirus
• 2019-nCoV Vaccine mRNA-1273

Topics

• 2019-nCoV Vaccine mRNA-1273
• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• COVID-19 (immunology, virology)
• COVID-19 Vaccines (immunology)
• Cell Line
• Chlorocebus aethiops
• Female
• Humans
• Macaca mulatta
• Male
• Mesocricetus
• Primates (immunology, virology)
• RNA, Viral (immunology)
• SARS-CoV-2 (immunology)
• Spike Glycoprotein, Coronavirus (immunology)
• Vaccination (methods)
• Vero Cells
• Viral Load (methods)