tetano
Editor, Senior Moderator
Antiviral Res
. 2024 Mar 4:105854.
doi: 10.1016/j.antiviral.2024.105854. Online ahead of print. A virus-like particle candidate vaccine based on CRISPR/Cas9 gene editing technology elicits broad-spectrum protection against SARS-CoV-2
Weiqi Wang[SUP] 1 [/SUP], Shen Wang[SUP] 2 [/SUP], Xianyong Meng[SUP] 3 [/SUP], Yongkun Zhao[SUP] 2 [/SUP], Nan Li[SUP] 2 [/SUP], Tiecheng Wang[SUP] 2 [/SUP], Na Feng[SUP] 4 [/SUP], Feihu Yan[SUP] 5 [/SUP], Xianzhu Xia[SUP] 6 [/SUP]
Affiliations
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 (ALVAC-VLPs) 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.
Keywords: CRISPR/Cas9; Canarypox-virus vector; Cellular immunity; Cross-neutralizing antibody; Toll-like receptor 4; Virus-like particle vaccine.
. 2024 Mar 4:105854.
doi: 10.1016/j.antiviral.2024.105854. Online ahead of print. A virus-like particle candidate vaccine based on CRISPR/Cas9 gene editing technology elicits broad-spectrum protection against SARS-CoV-2
Weiqi Wang[SUP] 1 [/SUP], Shen Wang[SUP] 2 [/SUP], Xianyong Meng[SUP] 3 [/SUP], Yongkun Zhao[SUP] 2 [/SUP], Nan Li[SUP] 2 [/SUP], Tiecheng Wang[SUP] 2 [/SUP], Na Feng[SUP] 4 [/SUP], Feihu Yan[SUP] 5 [/SUP], Xianzhu Xia[SUP] 6 [/SUP]
Affiliations
- PMID: 38447647
- DOI: 10.1016/j.antiviral.2024.105854
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 (ALVAC-VLPs) 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.
Keywords: CRISPR/Cas9; Canarypox-virus vector; Cellular immunity; Cross-neutralizing antibody; Toll-like receptor 4; Virus-like particle vaccine.