دورية أكاديمية

Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.

التفاصيل البيبلوغرافية
العنوان: Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.
المؤلفون: Lee J; Department of Biochemistry, University of Washington, Seattle, WA, USA., Zepeda SK; Department of Biochemistry, University of Washington, Seattle, WA, USA., Park YJ; Department of Biochemistry, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA., Taylor AL; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Quispe J; Department of Biochemistry, University of Washington, Seattle, WA, USA., Stewart C; Department of Biochemistry, University of Washington, Seattle, WA, USA., Leaf EM; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Treichel C; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Corti D; Humabs Biomed SA, a Subsidiary of Vir. Biotechnology, 6500 Bellinzona, Switzerland., King NP; Department of Biochemistry, University of Washington, Seattle, WA, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Starr TN; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Veesler D; Department of Biochemistry, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.
المصدر: Cell host & microbe [Cell Host Microbe] 2023 Dec 13; Vol. 31 (12), pp. 1961-1973.e11. Date of Electronic Publication: 2023 Nov 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, Mass. : Cell Press
مواضيع طبية MeSH: Severe acute respiratory syndrome-related coronavirus* , Chiroptera*, Animals ; Humans ; Angiotensin-Converting Enzyme 2 ; SARS-CoV-2/genetics ; Tropism ; Spike Glycoprotein, Coronavirus ; Antibodies, Viral
مستخلص: Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.
Competing Interests: Declaration of interests N.P.K. and D.V. are named as inventors on patents for coronavirus nanoparticle vaccines filed by the University of Washington. N.P.K. is a co-founder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. and has received an unrelated sponsored research agreement from Pfizer. D.C. is an employee of Vir Biotechnology and may hold shares in Vir Biotechnology. T.N.S. consults for Apriori Bio on DMS. The lab of T.N.S. has received sponsored research agreements unrelated to the present work from Vir Biotechnology and Aerium Therapeutics, Inc. T.N.S. may receive a share of intellectual property revenue as inventor on a Fred Hutchinson Cancer Center-optioned patent related to stabilization of SARS-CoV-2 RBDs. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
التعليقات: Update of: bioRxiv. 2023 Sep 13;:. (PMID: 37745523)
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معلومات مُعتمدة: DP1 AI158186 United States AI NIAID NIH HHS; F31 AI174573 United States AI NIAID NIH HHS; P01 AI167966 United States AI NIAID NIH HHS; S10 OD026959 United States OD NIH HHS; K99 AI166250 United States AI NIAID NIH HHS; S10 OD021644 United States OD NIH HHS; 75N93022C00036 United States AI NIAID NIH HHS; T32 GM008268 United States GM NIGMS NIH HHS; P30 CA042014 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: ACE2; PRD-0038; SARS-CoV-2; bat coronaviruses; clade 3 sarbecovirus; cryo-EM; receptor tropism; spike glycoprotein; vaccine; zoonotic spillover
المشرفين على المادة: EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
0 (Spike Glycoprotein, Coronavirus)
0 (Antibodies, Viral)
تواريخ الأحداث: Date Created: 20231121 Date Completed: 20231216 Latest Revision: 20240308
رمز التحديث: 20240308
مُعرف محوري في PubMed: PMC10913562
DOI: 10.1016/j.chom.2023.10.018
PMID: 37989312
قاعدة البيانات: MEDLINE
الوصف
تدمد:1934-6069
DOI:10.1016/j.chom.2023.10.018