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

Corbett, Kizzmekia S; Werner, Anne P; Connell, Sarah O'; Gagne, Matthew; Lai, Lilin; Moliva, Juan I; Flynn, Barbara; Choi, Angela; Koch, Matthew; Foulds, Kathryn E; Andrew, Shayne F; Flebbe, Dillon R; Lamb, Evan; Nurmukhambetova, Saule T; Provost, Samantha J; Bock, Kevin W; Minai, Mahnaz; Nagata, Bianca M; Ry, Alex Van; Flinchbaugh, Zackery; Johnston, Timothy S; Mokhtari, Elham Bayat; Mudvari, Prakriti; Henry, Amy R; Laboune, Farida; Chang, Becky; Porto, Maciel; Wear, Jaclyn; Alvarado, Gabriela S; Boyoglu-Barnum, Seyhan; Todd, John-Paul M; Bart, Bridget; Cook, Anthony; Dodson, Alan; Pessaint, Laurent; Steingrebe, Katelyn; Elbashir, Sayda; Sriparna, Manjari; Pekosz, Andrew; Andersen, Hanne; Wu, Kai; Edwards, Darin K; Kar, Swagata; Lewis, Mark G; Boritz, Eli; Moore, Ian N; Carfi, Andrea; Suthar, Mehul S; McDermott, Adrian; Roederer, Mario

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.