Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations

Dussupt, Vincent; Sankhala, Rajeshwer S.; Mendez-Rivera, Letzibeth; Townsley, Samantha M.; Schmidt, Fabian; Wieczorek, Lindsay; Lal, Kerri G.; Donofrio, Gina C.; Tran, Ursula; Jackson, Nathaniel D.; Zaky, Weam I.; Zemil, Michelle; Tritsch, Sarah R.; Chen, Wei-Hung; Martinez, Elizabeth J.; Ahmed, Aslaa; Choe, Misook; Chang, William C.; Hajduczki, Agnes; Jian, Ningbo; Peterson, Caroline E.; Rees, Phyllis A.; Rutkowska, Magdalena; Slike, Bonnie M.; Selverian, Christopher N.; Swafford, Isabella; Teng, I-Ting; Thomas, Paul V.; Zhou, Tongqing; Smith, Clayton J.; Currier, Jeffrey R.; Kwong, Peter D.; Rolland, Morgane; Davidson, Edgar; Doranz, Benjamin J.; Mores, Christopher N.; Hatziioannou, Theodora; Reiley, William W.; Bieniasz, Paul D.; Paquin-Proulx, Dominic; Gromowski, Gregory D.; Polonis, Victoria R.; Michael, Nelson L.; Modjarrad, Kayvon; Joyce, M. Gordon; Krebs, Shelly J.

doi:10.1038/s41590-021-01068-z

Title: Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations

Journal Article · 29 October 2021 · Nature Immunology

DOI: https://doi.org/10.1038/s41590-021-01068-z · OSTI ID:1837258

^[1]; Sankhala, Rajeshwer S. ^[1]; Mendez-Rivera, Letzibeth ^[1]; Townsley, Samantha M. ^[1]; Schmidt, Fabian ^[2]; Wieczorek, Lindsay ^[1]; Lal, Kerri G. ^[1]; Donofrio, Gina C. ^[1]; Tran, Ursula ^[1];

^[1]; Zaky, Weam I. ^[1];

^[1]; Tritsch, Sarah R. ^[3]; Chen, Wei-Hung ^[1]; Martinez, Elizabeth J. ^[1];

^[4]; Choe, Misook ^[1];

^[1]; Hajduczki, Agnes ^[1]; Jian, Ningbo ^[1] more »

Walter Reed Army Institute of Research, Silver Spring, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD (United States)
Rockefeller Univ., New York, NY (United States)
George Washington Univ., Washington, DC (United States)
Walter Reed Army Institute of Research, Silver Spring, MD (United States)
Integral Molecular, Philadelphia, PA (United States)
National Institutes of Health (NIH), Bethesda, MD (United States). National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health (NIH), Bethesda, MD (United States). National Cancer Institute (NCI)
Trudeau Institute, Saranac Lake, NY (United States)

Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); USDOD; Vaccine Research Center; National Institutes of Health (NIH); National Cancer Institute

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1837258

Journal Information:: Nature Immunology, Journal Name: Nature Immunology Journal Issue: 12 Vol. 22; ISSN 1529-2908

Publisher:: Nature Research, Springer NatureCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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