Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response.

Humans Antibodies, Neutralizing SARS-CoV-2 / genetics COVID-19 Antibodies, Monoclonal Epitopes Neutralization Tests

COVID-19 SARS-CoV-2 variants cryo-EM structure human monoclonal antibodies neutralizing antibodies shared antibody response

Journal

Structure (London, England : 1993)

ISSN: 1878-4186

Titre abrégé: Structure

Pays: United States

ID NLM: 101087697

Informations de publication

Date de publication:
06 Jul 2023

Historique:

received: 09 11 2022

revised: 09 03 2023

accepted: 21 04 2023

medline: 10 7 2023

pubmed: 12 5 2023

entrez: 11 5 2023

Statut: ppublish

Résumé

Understanding the molecular features of neutralizing epitopes is important for developing vaccines/therapeutics against emerging SARS-CoV-2 variants. We describe three monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during the first wave of the pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, poorly neutralized Beta, and failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these mAbs in complex with trimeric spike protein showed that all three mAbs bivalently bind spike with two mAbs targeting class 1 and one targeting a class 4 receptor binding domain epitope. The immunogenetic makeup, structure, and function of these mAbs revealed specific molecular interactions associated with the potent multi-variant binding/neutralization efficacy. This knowledge shows how mutational combinations can affect the binding or neutralization of an antibody, which in turn relates to the efficacy of immune responses to emerging SARS-CoV-2 escape variants.

Identifiants

DOI: 10.1016/j.str.2023.04.010 PMID: 37167972 PMC: PMC10171968

pubmed: 37167972

pii: S0969-2126(23)00133-8

doi: 10.1016/j.str.2023.04.010

pmc: PMC10171968

pii:

doi:

Substances chimiques

Antibodies, Neutralizing 0

Antibodies, Monoclonal 0

Epitopes 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

801-811.e5

Subventions

Organisme : NIGMS NIH HHS

ID : T32 GM142617

Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests The International Center for Genetic Engineering and Biotechnology, New Delhi, India, Emory Vaccine Center, Emory University, Atlanta, USA, Indian Council of Medical Research, India, and Department of Biotechnology, India, have filed a provisional patent application on human monoclonal antibodies mentioned in this study on which A.C., S.K., M.K.K., and A.S. are inventors (Indian patent 202111052088). N.C., H.P.V., A.S.N., and J.D.R. are co-inventors on a pending patent related to SARS-CoV-2 WT, Delta, and Omicron spike protein structures and ACE2 Interactions from BoAb assay technology filed by Emory University (US patent application no. 63/265,361, filed on December 14, 2021). M.S.S. has previously served as a consultant for Moderna and Ocugen. J.D.R. is a co-founder and consultant for Cambium Medical Technologies. J.D.R. is a consultant for Secure Transfusion Services. All other authors declare no competing interests.