دورية أكاديمية
أعرض في EDS

Convergence of immune escape strategies highlights plasticity of SARS-CoV-2 spike.

التفاصيل البيبلوغرافية
العنوان: Convergence of immune escape strategies highlights plasticity of SARS-CoV-2 spike.
المؤلفون: Yu X; Structural & Protein Sciences, Janssen Research and Development, Spring House, Pennsylvania, United States of America., Juraszek J; Janssen Vaccines & Prevention BV, Leiden, the Netherlands., Rutten L; Janssen Vaccines & Prevention BV, Leiden, the Netherlands., Bakkers MJG; Janssen Vaccines & Prevention BV, Leiden, the Netherlands., Blokland S; Janssen Vaccines & Prevention BV, Leiden, the Netherlands., Melchers JM; Janssen Vaccines & Prevention BV, Leiden, the Netherlands., van den Broek NJF; Janssen Vaccines & Prevention BV, Leiden, the Netherlands., Verwilligen AYW; Janssen Vaccines & Prevention BV, Leiden, the Netherlands., Abeywickrema P; Structural & Protein Sciences, Janssen Research and Development, Spring House, Pennsylvania, United States of America., Vingerhoets J; Janssen Pharmaceutica N.V., Clinical Microbiology and Immunology, Beerse, Belgium., Neefs JM; Janssen Pharmaceutica N.V., Discovery Sciences, Beerse, Belgium., Bakhash SAM; Department of Laboratory Medicine and Pathology, Virology Division, University of Washington, Seattle, Washington, United States of America., Roychoudhury P; Department of Laboratory Medicine and Pathology, Virology Division, University of Washington, Seattle, Washington, United States of America., Greninger A; Department of Laboratory Medicine and Pathology, Virology Division, University of Washington, Seattle, Washington, United States of America., Sharma S; Structural & Protein Sciences, Janssen Research and Development, Spring House, Pennsylvania, United States of America., Langedijk JPM; Janssen Vaccines & Prevention BV, Leiden, the Netherlands.
المصدر: PLoS pathogens [PLoS Pathog] 2023 May 01; Vol. 19 (5), pp. e1011308. Date of Electronic Publication: 2023 May 01 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: COVID-19*, Humans ; SARS-CoV-2/genetics ; Antibodies, Neutralizing ; Disulfides ; Immunotherapy ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Viral
مستخلص: The global spread of the SARS-CoV-2 virus has resulted in emergence of lineages which impact the effectiveness of immunotherapies and vaccines that are based on the early Wuhan isolate. All currently approved vaccines employ the spike protein S, as it is the target for neutralizing antibodies. Here we describe two SARS-CoV-2 isolates with unusually large deletions in the N-terminal domain (NTD) of the spike. Cryo-EM structural analysis shows that the deletions result in complete reshaping of the NTD supersite, an antigenically important region of the NTD. For both spike variants the remodeling of the NTD negatively affects binding of all tested NTD-specific antibodies in and outside of the NTD supersite. For one of the variants, we observed a P9L mediated shift of the signal peptide cleavage site resulting in the loss of a disulfide-bridge; a unique escape mechanism with high antigenic impact. Although the observed deletions and disulfide mutations are rare, similar modifications have become independently established in several other lineages, indicating a possibility to become more dominant in the future. The observed plasticity of the NTD foreshadows its broad potential for immune escape with the continued spread of SARS-CoV-2.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: J.J., L.R., M.J.G.B., and J.P.L. are co-inventors on related vaccine patents. X.Y., J.J., L.R., M.J.G.B., J.J.M., S.B., N.J.F.vdB., A.Y.W.V., P.A., J.V., J.N., S.S., and J.P.L. are employees of Janssen Vaccines & Prevention BV. X.Y., J.J., L.R., J.V., and J.P.L. hold stock of Johnson & Johnson.
(Copyright: © 2023 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: 0 (Antibodies, Neutralizing)
0 (Disulfides)
0 (Spike Glycoprotein, Coronavirus)
0 (Antibodies, Viral)
0 (spike protein, SARS-CoV-2)
تواريخ الأحداث: Date Created: 20230501 Date Completed: 20230515 Latest Revision: 20230519
رمز التحديث: 20230520
مُعرف محوري في PubMed: PMC10174534
DOI: 10.1371/journal.ppat.1011308
PMID: 37126534
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1011308