دورية أكاديمية
أعرض في EDS

Targeting the Spike Receptor Binding Domain Class V Cryptic Epitope by an Antibody with Pan-Sarbecovirus Activity.

التفاصيل البيبلوغرافية
العنوان: Targeting the Spike Receptor Binding Domain Class V Cryptic Epitope by an Antibody with Pan-Sarbecovirus Activity.
المؤلفون: Jensen JL; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Sankhala RS; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Dussupt V; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Bai H; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Hajduczki A; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Lal KG; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Chang WC; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Martinez EJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Peterson CE; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Golub ES; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Rees PA; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Mendez-Rivera L; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Zemil M; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Kavusak E; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Mayer SV; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Wieczorek L; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Kannan S; Integral Molecular, Philadelphia, Pennsylvania, USA., Doranz BJ; Integral Molecular, Philadelphia, Pennsylvania, USA., Davidson E; Integral Molecular, Philadelphia, Pennsylvania, USA., Yang ES; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Zhang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Chen M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Choe M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Gromowski GD; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Koup RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Michael NL; Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Polonis VR; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Rolland M; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Modjarrad K; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Krebs SJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Joyce MG; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
المصدر: Journal of virology [J Virol] 2023 Jul 27; Vol. 97 (7), pp. e0159622. Date of Electronic Publication: 2023 Jul 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington Dc : American Society For Microbiology
Original Publication: Baltimore, American Society for Microbiology.
مواضيع طبية MeSH: Antibodies, Viral*/chemistry , Antibodies, Viral*/metabolism , COVID-19* , Epitopes*/chemistry , Severe acute respiratory syndrome-related coronavirus*/chemistry, Humans ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/metabolism ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/metabolism ; SARS-CoV-2/chemistry ; SARS-CoV-2/metabolism ; Protein Domains ; Crystallography, X-Ray ; Protein Structure, Quaternary ; Models, Molecular ; Cell Line
مستخلص: Novel therapeutic monoclonal antibodies (MAbs) must accommodate comprehensive breadth of activity against diverse sarbecoviruses and high neutralization potency to overcome emerging variants. Here, we report the crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) in complex with MAb WRAIR-2063, a moderate-potency neutralizing antibody with exceptional sarbecovirus breadth, that targets the highly conserved cryptic class V epitope. This epitope overlaps substantially with the spike protein N-terminal domain (NTD) -interacting region and is exposed only when the spike is in the open conformation, with one or more RBDs accessible. WRAIR-2063 binds the RBD of SARS-CoV-2 WA-1, all variants of concern (VoCs), and clade 1 to 4 sarbecoviruses with high affinity, demonstrating the conservation of this epitope and potential resiliency against variation. We compare structural features of additional class V antibodies with their reported neutralization capacity to further explore the utility of the class V epitope as a pan-sarbecovirus vaccine and therapeutic target. IMPORTANCE Characterization of MAbs against SARS-CoV-2, elicited through vaccination or natural infection, has provided vital immunotherapeutic options for curbing the COVID-19 pandemic and has supplied critical insights into SARS-CoV-2 escape, transmissibility, and mechanisms of viral inactivation. Neutralizing MAbs that target the RBD but do not block ACE2 binding are of particular interest because the epitopes are well conserved within sarbecoviruses and MAbs targeting this area demonstrate cross-reactivity. The class V RBD-targeted MAbs localize to an invariant site of vulnerability, provide a range of neutralization potency, and exhibit considerable breadth against divergent sarbecoviruses, with implications for vaccine and therapeutic development.
Competing Interests: The authors declare a conflict of interest. Patent application number PCT/US 63/140,763, PCT WO 2022/159839 A1 was filed containing the mAbs described in this publication for authors S.J.K., K.M., V.D., and N.L.M. M.G.J. and K.M. are named as inventors on international patent application 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 WO/2018/081318 and U.S. patent 10,960,070 entitled “Prefusion coronavirus spike proteins and their use.” The other authors declare no competing interests.
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معلومات مُعتمدة: P41 GM103403 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: COVID-19; SARS-CoV; SARS-CoV-2; X-ray crystallography; betacoronaviruses; convalescent; cryptic; epitope; neutralizing antibodies; receptor binding domain; sarbecoviruses; spike; structural biology; variants of concern
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
0 (Epitopes)
تواريخ الأحداث: Date Created: 20230703 Date Completed: 20230801 Latest Revision: 20230801
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC10373542
DOI: 10.1128/jvi.01596-22
PMID: 37395646
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-5514
DOI:10.1128/jvi.01596-22