Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration
Dean Follmann, Meagan P. O’Brien, Jonathan Fintzi, Michael P. Fay, David C. Montefiori, Allyson Mateja, Gary Herman, Andrea T. Hooper, K. C. Turner, K.-C. Chan, Eduardo Forleo‐Neto, Flonza Isa, Lindsey R. Baden, Hana M. El Sahly, Holly Janes, Nicole A. Doria‐Rose, Jacqueline M. Miller, Honghong Zhou, Weiping Dang, David Benkeser, Youyi Fong, Peter B. Gilbert, Mary Marovich, Myron S. Cohen
Abstract
While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates of protection against COVID-19 in the casirivimab + imdevimab monoclonal antibody (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and in the mRNA-1273 vaccine trial (ClinicalTrials.gov #NCT04470427). In the mAb trial, protective efficacy of 92% (95% confidence interval (CI): 84%, 98%) is associated with a nAb titer of 1000 IU50/ml, with lower efficacy at lower nAb titers. In the vaccine trial, protective efficacies of 93% [95% CI: 91%, 95%] and 97% (95% CI: 95%, 98%) are associated with nAb titers of 100 and 1000 IU50/ml, respectively. These data quantitate a nAb titer correlate of protection for mAbs benchmarked alongside vaccine induced nAb titers and support nAb titer as a surrogate endpoint for authorizing new mAbs.