Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain.

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
16 Dec 2023
Historique:
received: 05 05 2023
revised: 14 09 2023
accepted: 30 11 2023
medline: 2 1 2024
pubmed: 2 1 2024
entrez: 29 12 2023
Statut: aheadofprint

Résumé

Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitope, and WRAIR-2123, the class I ACE2-binding site. The broad reactivity of class IV and V mAbs to conserved regions of SARS-CoV-2 VoCs and other sarbecovirus provides a framework for long-term immunotherapeutic development strategies.

Identifiants

DOI: 10.1016/j.str.2023.11.015 PMID: 38157856
pubmed: 38157856
pii: S0969-2126(23)00440-9
doi: 10.1016/j.str.2023.11.015
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Patent application number PCT/US 63/140,763 was filed containing mAbs described in this publication for authors S.J.K., K.M., V.D., S.M.T., G.D., and N.L.M. The status of the patent is pending, not yet published. M.G.J. and K.M. are named as inventors on International Patent Application No. WO 2021/178971 A1 entitled “Vaccines against SARS-CoV-2 and other coronaviruses.” M.G.J. is named as an inventor on International Patent Application No. WO/2018/081318 and U.S. patent 10,960,070 entitled “Prefusion Coronavirus S Proteins and Their Use.”

Auteurs

Rajeshwer S Sankhala (RS)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Vincent Dussupt (V)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Wei-Hung Chen (WH)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Hongjun Bai (H)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Elizabeth J Martinez (EJ)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Jaime L Jensen (JL)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Phyllis A Rees (PA)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Agnes Hajduczki (A)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

William C Chang (WC)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Misook Choe (M)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Lianying Yan (L)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Spencer L Sterling (SL)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Isabella Swafford (I)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Caitlin Kuklis (C)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Sandrine Soman (S)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Jocelyn King (J)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Courtney Corbitt (C)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Michelle Zemil (M)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Caroline E Peterson (CE)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Letzibeth Mendez-Rivera (L)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Samantha M Townsley (SM)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Gina C Donofrio (GC)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Kerri G Lal (KG)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Ursula Tran (U)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Ethan C Green (EC)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Clayton Smith (C)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.

Natalia de Val (N)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.

Eric D Laing (ED)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Christopher C Broder (CC)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Jeffrey R Currier (JR)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Gregory D Gromowski (GD)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Lindsay Wieczorek (L)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Morgane Rolland (M)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Dominic Paquin-Proulx (D)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Dewald van Dyk (D)

Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Zachary Britton (Z)

Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Saravanan Rajan (S)

Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Yueh Ming Loo (YM)

Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Patrick M McTamney (PM)

Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Mark T Esser (MT)

Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Victoria R Polonis (VR)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Nelson L Michael (NL)

Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Shelly J Krebs (SJ)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic address: skrebs@hivresearch.org.

Kayvon Modjarrad (K)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

M Gordon Joyce (MG)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic address: gjoyce@eidresearch.org.

Classifications MeSH