In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains.

Chen, Rita E; Winkler, Emma S; Case, James Brett; Aziati, Ishmael D; Bricker, Traci L; Joshi, Astha; Darling, Tamarand L; Ying, Baoling; Errico, John M; Shrihari, Swathi; VanBlargan, Laura A; Xie, Xuping; Gilchuk, Pavlo; Zost, Seth J; Droit, Lindsay; Liu, Zhuoming; Stumpf, Spencer; Wang, David; Handley, Scott A; Stine, W Blaine; Shi, Pei-Yong; Davis-Gardner, Meredith E; Suthar, Mehul S; Knight, Miguel Garcia; Andino, Raul; Chiu, Charles Y; Ellebedy, Ali H; Fremont, Daved H; Whelan, Sean P J; Crowe, James E; Purcell, Lisa; Corti, Davide; Boon, Adrianus C M; Diamond, Michael S

Rapidly-emerging variants jeopardize antibody-based countermeasures against SARS-CoV-2. While cell culture experiments have demonstrated loss of potency of several anti-spike neutralizing antibodies against SARS-CoV-2 variant strains1-3, the in vivo significance of these results remains uncertain. Using a panel of monoclonal antibodies (mAbs) corresponding to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron, and Lilly, we report the impact on protection in animals against authentic SARS-CoV-2 variants including viruses with B.1.1.7, B.1.351, or B.1.1.28 spike genes. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1, and B.1.526 viruses with E484 spike protein mutations, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice, and hamsters without emergence of resistance. Exceptions were mAb LY-CoV555 and LY-CoV555/LY-CoV016 mono- and combination therapy, which lost all protective activity, and AbbVie 2B04/47D11, which showed partial loss of activity. When administered after infection as therapy, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Thus, many, but not all, of the antibody products with Emergency Use Authorization (EUA) should retain substantial efficacy against the prevailing SARS-CoV-2 variant strains.