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

Publication date: Mar 04, 2024

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.

Concepts Keywords
Canarypox Canarypox-virus vector
Lethal Cellular immunity
Lymphoid CRISPR/Cas9
Tlr4 Cross-neutralizing antibody
Vaccines Toll-like receptor 4
Virus-like particle vaccine

Semantics

Type Source Name
disease VO vaccine
disease VO gene
disease VO Severe acute respiratory syndrome coronavirus 2
disease VO effectiveness
pathway KEGG Coronavirus disease
disease MESH COVID-19
disease VO immunization
disease IDO cell
disease MESH weight loss
disease IDO immune response
disease VO Toll-like receptor 4
drug DRUGBANK Cycloserine
disease IDO production
disease VO COVID-19 vaccine
disease VO virus-like particle vaccine

Original Article

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