دورية أكاديمية

Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.

التفاصيل البيبلوغرافية
العنوان: Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.
المؤلفون: Hsieh CL; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA., Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Miller EH; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.; Department of Medicine-Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY, 10461, USA., Zhou L; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA., Powers JM; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Tse AL; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA., Wang A; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA., West A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Zweigart MR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Schisler JC; McAllister Heart Institute and Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Jangra RK; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.; Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA., Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA., Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., McLellan JS; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA. jmclellan@austin.utexas.edu.
المصدر: Nature communications [Nat Commun] 2024 Feb 20; Vol. 15 (1), pp. 1553. Date of Electronic Publication: 2024 Feb 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: SARS-CoV-2* , COVID-19*/prevention & control, Female ; Animals ; Humans ; Mice ; COVID-19 Vaccines ; Antigens, Viral/genetics ; Mice, Inbred BALB C ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Neutralizing ; Antibodies, Viral
مستخلص: Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.
(© 2024. The Author(s).)
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معلومات مُعتمدة: K12 TR004411 United States TR NCATS NIH HHS; P01 AI127335 United States AI NIAID NIH HHS; P20 GM134974 United States GM NIGMS NIH HHS; INV-031624 United States GATES Bill & Melinda Gates Foundation
المشرفين على المادة: 0 (COVID-19 Vaccines)
0 (spike protein, SARS-CoV-2)
0 (Antigens, Viral)
0 (Spike Glycoprotein, Coronavirus)
0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
SCR Organism: SARS-CoV-2 variants
تواريخ الأحداث: Date Created: 20240220 Date Completed: 20240222 Latest Revision: 20240603
رمز التحديث: 20240603
مُعرف محوري في PubMed: PMC10879192
DOI: 10.1038/s41467-024-45404-x
PMID: 38378768
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-45404-x