Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations.
Nat Immunol
; 22(12): 1503-1514, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1493136
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Antibodies, Monoclonal
Type of study:
Prognostic study
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Nat Immunol
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Affiliation country:
S41590-021-01068-z
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