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一种靶向严重急性呼吸综合征冠状病毒2(SARS-CoV-2)奥密克戎刺突蛋白的鼻内给药单克隆抗体对小鼠SARS-CoV-2奥密克戎感染的治疗干预

Therapeutic Intervention of an Intranasally Administered Monoclonal Antibody Targeting the SARS-CoV-2 Omicron Spike Protein Against SARS-CoV-2 Omicron Infection in Mice.

作者信息

Kim Jinsoo, Kim Suyeon, Kim Dongbum, Kim Minyoung, Baek Kyeongbin, Kang Bo Min, An Seungchan, Park In Guk, Kim Songrae, Park Sangkyu, Suh Jun Gyo, Noh Minsoo, Lee Younghee, Kwon Hyung-Joo

机构信息

Institute of Medical Science, College of Medicine, Hallym University, Chuncheon, Republic of Korea.

Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Republic of Korea.

出版信息

Viral Immunol. 2025 Jul-Aug;38(6):212-221. doi: 10.1089/vim.2024.0095. Epub 2025 Jun 4.

DOI:10.1089/vim.2024.0095
PMID:40465408
Abstract

SARS-CoV-2 has evolved into several variants of concern, with Omicron and its subvariants currently being the most prevalent. Previously, we developed a mouse monoclonal antibody (m1E3H12 mAb) specific to the receptor binding domain of SARS-CoV-2 Omicron spike protein, and the mAb showed neutralizing activity against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB. Here, we showed that the mAb provided protection against SARS-CoV-2 Omicron infection in K18-hACE2 transgenic mice when administered intranasally. The mAb treatment reduced viral loads in both the brain and lungs. Additionally, the elevated levels of RANTES (CCL5) and MIP-3 alpha (CCL20) in the brain following SARS-CoV-2 Omicron infection showed a decreasing trend after mAb treatment. Therefore, we conclude that our mAb specific to SARS-CoV-2 Omicron spike protein has the potential to be applied as therapeutics against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)已经进化出几种值得关注的变体,目前奥密克戎及其亚变体最为流行。此前,我们开发了一种针对SARS-CoV-2奥密克戎刺突蛋白受体结合域的小鼠单克隆抗体(m1E3H12 mAb),该单克隆抗体对SARS-CoV-2奥密克戎BA.1及其亚变体BA.5、BQ.1.1和XBB具有中和活性。在此,我们表明,当经鼻给药时,该单克隆抗体能保护K18-hACE2转基因小鼠免受SARS-CoV-2奥密克戎感染。单克隆抗体治疗降低了大脑和肺部的病毒载量。此外,SARS-CoV-2奥密克戎感染后大脑中升高的调节激活正常T细胞表达和分泌的趋化因子(RANTES,CCL5)和巨噬细胞炎性蛋白-3α(MIP-3α,CCL20)水平在单克隆抗体治疗后呈下降趋势。因此,我们得出结论,我们针对SARS-CoV-2奥密克戎刺突蛋白的单克隆抗体有潜力作为治疗药物用于对抗SARS-CoV-2奥密克戎BA.1及其亚变体BA.5、BQ.1.1和XBB。

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