TY - JOUR
T1 - Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations
AU - Dussupt, Vincent
AU - Sankhala, Rajeshwer S.
AU - Mendez-Rivera, Letzibeth
AU - Townsley, Samantha M.
AU - Schmidt, Fabian
AU - Wieczorek, Lindsay
AU - Lal, Kerri G.
AU - Donofrio, Gina C.
AU - Tran, Ursula
AU - Jackson, Nathaniel D.
AU - Zaky, Weam I.
AU - Zemil, Michelle
AU - Tritsch, Sarah R.
AU - Chen, Wei Hung
AU - Martinez, Elizabeth J.
AU - Ahmed, Aslaa
AU - Choe, Misook
AU - Chang, William C.
AU - Hajduczki, Agnes
AU - Jian, Ningbo
AU - Peterson, Caroline E.
AU - Rees, Phyllis A.
AU - Rutkowska, Magdalena
AU - Slike, Bonnie M.
AU - Selverian, Christopher N.
AU - Swafford, Isabella
AU - Teng, I. Ting
AU - Thomas, Paul V.
AU - Zhou, Tongqing
AU - Smith, Clayton J.
AU - Currier, Jeffrey R.
AU - Kwong, Peter D.
AU - Rolland, Morgane
AU - Davidson, Edgar
AU - Doranz, Benjamin J.
AU - Mores, Christopher N.
AU - Hatziioannou, Theodora
AU - Reiley, William W.
AU - Bieniasz, Paul D.
AU - Paquin-Proulx, Dominic
AU - Gromowski, Gregory D.
AU - Polonis, Victoria R.
AU - Michael, Nelson L.
AU - Modjarrad, Kayvon
AU - Joyce, M. Gordon
AU - Krebs, Shelly J.
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - https://www.nature.com/articles/s41590-021-01068-z
UR - http://www.scopus.com/inward/record.url?scp=85118323133&partnerID=8YFLogxK
U2 - 10.1038/s41590-021-01068-z
DO - 10.1038/s41590-021-01068-z
M3 - Article
SN - 1529-2908
VL - 22
SP - 1503
EP - 1514
JO - Nature Immunology
JF - Nature Immunology
IS - 12
ER -