Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 20. Feb., Seite 1553 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hsieh, Ching-Lin [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Neutralizing |
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| Anmerkungen: |
Date Completed 22.02.2024 Date Revised 13.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-45404-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368687880 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Leist, Sarah R |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Emily Happy |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Powers, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Tse, Alexandra L |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Albert |e verfasserin |4 aut | |
| 700 | 1 | |a West, Ande |e verfasserin |4 aut | |
| 700 | 1 | |a Zweigart, Mark R |e verfasserin |4 aut | |
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| 700 | 1 | |a Jangra, Rohit K |e verfasserin |4 aut | |
| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
| 700 | 1 | |a Baric, Ralph S |e verfasserin |4 aut | |
| 700 | 1 | |a McLellan, Jason S |e verfasserin |4 aut | |
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