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单价和三价基于水疱性口炎病毒的COVID-19疫苗可引发针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变体的中和抗体和CD8 T细胞。

Monovalent and trivalent VSV-based COVID-19 vaccines elicit neutralizing antibodies and CD8 T cells against SARS-CoV-2 variants.

作者信息

Parham Kate A, Kim Gyoung Nyoun, Richer Connor G, Ninkov Marina, Wu Kunyu, Saeedian Nasrin, Li Yue, Rashu Rasheduzzaman, Barr Stephen D, Arts Eric J, Haeryfar S M Mansour, Kang C Yong, Troyer Ryan M

机构信息

Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 3K7, Canada.

出版信息

iScience. 2023 Apr 21;26(4):106292. doi: 10.1016/j.isci.2023.106292. Epub 2023 Feb 28.

Abstract

Recombinant vesicular stomatitis virus (rVSV) vaccines expressing spike proteins of Wuhan, Beta, and/or Delta variants of SARS-CoV-2 were generated and tested for induction of antibody and T cell immune responses following intramuscular delivery to mice. rVSV-Wuhan and rVSV-Delta vaccines and an rVSV-Trivalent (mixed rVSV-Wuhan, -Beta, -Delta) vaccine elicited potent neutralizing antibodies (nAbs) against live SARS-CoV-2 Wuhan (USAWA1), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529) viruses. Prime-boost vaccination with rVSV-Beta was less effective in this capacity. Heterologous boosting of rVSV-Wuhan with rVSV-Delta induced strong nAb responses against Delta and Omicron viruses, with the rVSV-Trivalent vaccine consistently effective in inducing nAbs against all the SARS-CoV-2 variants tested. All vaccines, including rVSV-Beta, elicited a spike-specific immunodominant CD8 T cell response. Collectively, rVSV vaccines targeting SARS-CoV-2 variants of concern may be considered in the global fight against COVID-19.

摘要

构建了表达严重急性呼吸综合征冠状病毒2(SARS-CoV-2)武汉株、贝塔株和/或德尔塔株刺突蛋白的重组水疱性口炎病毒(rVSV)疫苗,并在肌肉注射给小鼠后测试其诱导抗体和T细胞免疫反应的能力。rVSV-武汉株疫苗、rVSV-德尔塔株疫苗和rVSV-三价(rVSV-武汉株、-贝塔株、-德尔塔株混合)疫苗诱导产生了针对活的SARS-CoV-2武汉株(USAWA1)、贝塔株(B.1.351)、德尔塔株(B.1.617.2)和奥密克戎株(B.1.1.529)病毒的强效中和抗体(nAbs)。用rVSV-贝塔株进行初免-加强免疫在这方面效果较差。用rVSV-德尔塔株对rVSV-武汉株进行异源加强免疫诱导产生了针对德尔塔株和奥密克戎株病毒的强烈nAb反应,rVSV-三价疫苗始终能有效诱导产生针对所有测试的SARS-CoV-2变异株的nAbs。所有疫苗,包括rVSV-贝塔株疫苗,都引发了刺突特异性免疫显性CD8 T细胞反应。总体而言,在全球抗击2019冠状病毒病(COVID-19)的斗争中,可以考虑使用针对SARS-CoV-2关注变异株的rVSV疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7026/10156611/ae7c1abafe58/fx1.jpg

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