A virus-like particle candidate vaccine based on CRISPR/Cas9 gene editing technology elicits broad-spectrum protection against SARS-CoV-2

文献类型： 外文期刊

第一作者： Wang, Weiqi

作者： Wang, Weiqi;Xia, Xianzhu;Wang, Weiqi;Wang, Shen;Meng, Xianyong;Zhao, Yongkun;Li, Nan;Wang, Tiecheng;Feng, Na;Yan, Feihu;Xia, Xianzhu;Meng, Xianyong

作者机构：

关键词： CRISPR/Cas9; Canarypox-virus vector; Virus -like particle vaccine; Cross -neutralizing antibody; Cellular immunity; Toll -like receptor 4

期刊名称：ANTIVIRAL RESEARCH （ 影响因子：7.6； 五年影响因子：5.8 ）

ISSN： 0166-3542

年卷期： 2024 年 225 卷

页码：

收录情况： SCI

摘要： The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with frequent mutations has seriously damaged the effectiveness of the 2019 coronavirus disease (COVID-19) vaccine. There is an urgent need to develop a broad-spectrum vaccine while elucidating the underlying immune mechanisms. Here, we developed a SARS-CoV-2 virus -like particles (VLPs) vaccine based on the Canarypox-virus vector (ALVACVLPs) using CRISPR/Cas9. Immunization with ALVAC-VLPs showed the effectively induce SARS-CoV-2 specific T and B cell responses to resist the lethal challenge of mouse adaptive strains. Notably, ALVAC-VLPs conferred protection in golden hamsters against SARS-CoV-2 Wuhan -Hu -1 (wild -type, WT) and variants (Beta, Delta, Omicron BA.1, and BA.2), as evidenced by the prevention of weight loss, reduction in lung and turbinate tissue damage, and decreased viral load. Further investigation into the mechanism of immune response induced by ALVAC-VLPs revealed that toll -like receptor 4 (TLR4) mediates the recruitment of dendritic cells (DCs) to secondary lymphoid organs, thereby initiating follicle assisted T (Tfh) cell differentiation, the proliferation of germinal center (GC) B cells and plasma cell production. These findings demonstrate the immunogenicity and efficacy of the safe ALVAC-VLPs vaccine against SARS-CoV-2 and provide valuable insight into the development of COVID-19 vaccine strategies.

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