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.

Here the authors assess neutralizing antibody (nAb) levels as correlate of protection in a monoclonal antibody prevention trial and a vaccine trial for COVID-19 and show that nAb titers correlate with clinical protection against COVID-19 supporting nAb titer as a surrogate endpoint for authorization of monoclonal antibodies.

Details

Title
Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration
Author
Follmann, Dean 1   VIAFID ORCID Logo  ; O’Brien, Meagan P. 2 ; Fintzi, Jonathan 1 ; Fay, Michael P. 1   VIAFID ORCID Logo  ; Montefiori, David 3 ; Mateja, Allyson 4 ; Herman, Gary A. 2 ; Hooper, Andrea T. 2 ; Turner, Kenneth C. 2 ; Chan, Kuo- Chen 2   VIAFID ORCID Logo  ; Forleo-Neto, Eduardo 2   VIAFID ORCID Logo  ; Isa, Flonza 2 ; Baden, Lindsey R. 5 ; El Sahly, Hana M. 6 ; Janes, Holly 7 ; Doria-Rose, Nicole 8   VIAFID ORCID Logo  ; Miller, Jacqueline 9 ; Zhou, Honghong 9 ; Dang, Weiping 9 ; Benkeser, David 10   VIAFID ORCID Logo  ; Fong, Youyi 11 ; Gilbert, Peter B. 11 ; Marovich, Mary 12 ; Cohen, Myron S. 13 

1  National Institutes of Health, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
2  Regeneron Pharmaceuticals, Inc., Tarrytown, USA (GRID:grid.418961.3) (ISNI:0000 0004 0472 2713) 
3  Duke University Medical Center, Department of Surgery, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216) 
4  Frederick National Laboratory for Cancer Research, Clinical Monitoring Research Program Directorate, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394) 
5  Brigham and Women’s Hospital, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
6  Baylor College of Medicine, Department of Molecular Virology and Microbiology, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
7  Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
8  National Institutes of Health, Vaccine Research Center, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
9  Moderna, Inc., Cambridge, USA (GRID:grid.479574.c) (ISNI:0000 0004 1791 3172) 
10  Emory University, Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
11  Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Washington, Department of Biostatistics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
12  National Institutes of Health, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, USA (GRID:grid.419681.3) (ISNI:0000 0001 2164 9667) 
13  The University of North Carolina at Chapel Hill, Institute for Global Health and Infectious Diseases, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000000122483208) 
Pages
3605
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-023-39292-w
ProQuest document ID
2827014221
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.