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Recombinant OC43 SARS-CoV-2 spike replacement virus: An improved BSL-2 proxy virus for SARS-CoV-2 neutralization assays

  1. Author:
    Hu, Zhe [ORCID]
    López-Muñoz, Alberto Domingo [ORCID]
    Kosik, Ivan [ORCID]
    Li, Tiansheng
    Callahan, Victoria
    Brooks, Kelsie [ORCID]
    Yee, Debra S
    Holly, Jaroslav
    Santos, Jefferson J S [ORCID]
    Castro Brant,Ayslan [ORCID]
    Johnson, Reed F [ORCID]
    Takeda, Kazuyo
    Zheng,Zhi-Ming [ORCID]
    Brenchley, Jason M [ORCID]
    Yewdell, Jonathan W
    Fox, Julie M [ORCID]

  2. Author Address

    Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., Barrier Immunity Section, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, NIH, Frederick, MD 21702., SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993.,
    1. Year: 2024
    2. Date: Jul 16
    3. Epub Date: 2024 07 08
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 121
    2. 29
    3. Pages: e2310421121
  4. Type of Article: Article
  5. Article Number: e2310421121
  1. Abstract:

    We generated a replication-competent OC43 human seasonal coronavirus (CoV) expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in place of the native spike (rOC43-CoV2 S). This virus is highly attenuated relative to OC43 and SARS-CoV-2 in cultured cells and animals and is classified as a biosafety level 2 (BSL-2) agent by the NIH biosafety committee. Neutralization of rOC43-CoV2 S and SARS-CoV-2 by S-specific monoclonal antibodies and human sera is highly correlated, unlike recombinant vesicular stomatitis virus-CoV2 S. Single-dose immunization with rOC43-CoV2 S generates high levels of neutralizing antibodies against SARS-CoV-2 and fully protects human ACE2 transgenic mice from SARS-CoV-2 lethal challenge, despite nondetectable replication in respiratory and nonrespiratory organs. rOC43-CoV2 S induces S-specific serum and airway mucosal immunoglobulin A and IgG responses in rhesus macaques. rOC43-CoV2 S has enormous value as a BSL-2 agent to measure S-specific antibodies in the context of a bona fide CoV and is a candidate live attenuated SARS-CoV-2 mucosal vaccine that preferentially replicates in the upper airway.

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External Sources

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  2. DOI: 10.1073/pnas.2310421121
  3. PMID: 38976733

Library Notes

  1. Fiscal Year: FY2023-2024
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