Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2310421121. doi: 10.1073/pnas.2310421121. Epub 2024 Jul 8.
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.
我们构建了一株能够复制的 OC43 季节性人类冠状病毒（CoV），其 Spike 蛋白被 SARS-CoV-2 的 Spike 蛋白取代（rOC43-CoV2 S）。与 OC43 和 SARS-CoV-2 相比，该病毒在细胞和动物中具有高度减毒特性，并且被 NIH 生物安全委员会归类为生物安全级别 2（BSL-2）试剂。rOC43-CoV2 S 和 SARS-CoV-2 的中和作用与 S 特异性单克隆抗体和人血清高度相关，与重组水疱性口炎病毒-CoV2 S 不同。单次免疫 rOC43-CoV2 S 可产生针对 SARS-CoV-2 的高水平中和抗体，并完全保护人 ACE2 转基因小鼠免受 SARS-CoV-2 的致命攻击，尽管在呼吸道和非呼吸道器官中无法检测到复制。rOC43-CoV2 S 可诱导恒河猴产生 S 特异性血清和气道黏膜免疫球蛋白 A 和 IgG 反应。rOC43-CoV2 S 作为 BSL-2 试剂具有巨大的价值，可在真正的 CoV 背景下测量 S 特异性抗体，并且是一种候选的活减毒 SARS-CoV-2 黏膜疫苗，优先在上呼吸道复制。
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