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

• 成果类型: Article
• 署名作者: Hu, Zhe; Lopez-Munoz, Alberto Domingo; Kosik, Ivan; Li, Tiansheng; Callahan, Victoria; Brooks, Kelsie; Yee, Debra S.; Holly, Jaroslav; Santos, Jefferson J. S.; Brant, Ayslan Castro; Johnson, Reed F.; Takeda, Kazuyo; Zheng, Zhi - Ming; Brenchley, Jason M.; Yewdell, Jonathan W.; Fox, Julie M.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); US Food & Drug Administration (FDA); Center for Biologics Evaluation & Research (CBER)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11355
• DOI: 10.1073/pnas.2310421121
• 发表日期: 2024-07-16
• 关键词: coronavirus; vaccine; infection

摘要

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