PDF(Pubmed)
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.
摘要：
我们产生了具有复制能力的OC43人类季节性冠状病毒（CoV），其表达了严重的急性呼吸道综合症冠状病毒2（SARS-CoV-2）尖峰，代替了天然尖峰（rOC43-CoV2S）。该病毒在培养的细胞和动物中相对于OC43和SARS-CoV-2是高度减毒的,并且被NIH生物安全委员会分类为生物安全2级(BSL-2)试剂。S特异性单克隆抗体对rOC43-CoV2S和SARS-CoV-2的中和与人血清高度相关,与重组水泡性口炎病毒-CoV2S不同。用rOC43-CoV2S单剂量免疫产生高水平的抗SARS-CoV-2的中和抗体，并完全保护人ACE2转基因小鼠免受SARS-CoV-2致命攻击，尽管在呼吸和非呼吸器官中检测不到复制。rOC43-CoV2S诱导恒河猴的S特异性血清和气道粘膜免疫球蛋白A和IgG反应。rOC43-CoV2S作为BSL-2试剂在真正的CoV的情况下测量S特异性抗体具有巨大价值，并且是候选的减毒SARS-CoV-2粘膜疫苗，优先在上呼吸道复制。
