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Structural basis for broad sarbecovirus neutralization by a human monoclonal antibody
- Source :
- bioRxiv, article-version (status) pre, article-version (number) 1
- Publication Year :
- 2021
- Publisher :
- Cold Spring Harbor Laboratory, 2021.
-
Abstract
- The recent emergence of SARS-CoV-2 variants of concern (VOC) and the recurrent spillovers of coronaviruses in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2×259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus clades. S2×259 broadly neutralizes spike-mediated entry of SARS-CoV-2 including the B.1.1.7, B.1.351, P.1 and B.1.427/B.1.429 VOC, as well as a wide spectrum of human and zoonotic sarbecoviruses through inhibition of ACE2 binding to the RBD. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2×259 possesses a remarkably high barrier to the emergence of resistance mutants. We show that prophylactic administration of S2×259 protects Syrian hamsters against challenges with the prototypic SARS-CoV-2 and the B.1.351 variant, suggesting this mAb is a promising candidate for the prevention and treatment of emergent VOC and zoonotic infections. Our data unveil a key antigenic site targeted by broadly-neutralizing antibodies and will guide the design of pan-sarbecovirus vaccines.
- Subjects :
- medicine.drug_class
Population
Cross Reactions
Monoclonal antibody
Antibodies, Viral
Viral Zoonoses
Epitope
Antigenic drift
Neutralization
Article
Antigen
Neutralization Tests
medicine
Animals
Humans
education
Immune Evasion
education.field_of_study
biology
Zoonotic Infection
Mesocricetus
SARS-CoV-2
Antibodies, Monoclonal
COVID-19
Virology
Disease Models, Animal
Mutation
biology.protein
Female
Antibody
Broadly Neutralizing Antibodies
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- bioRxiv
- Accession number :
- edsair.doi.dedup.....5306585f6250e97d4520b08446d06de3