A virus-like particle candidate vaccine based on CRISPR/Cas9 gene editing technology elicits broad-spectrum...

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose a significant threat to existing COVID-19 vaccine efficacy.
• There is a critical need for broad-spectrum vaccines and a deeper understanding of immune responses against SARS-CoV-2.

Purpose of the Study:

• To develop and evaluate a novel SARS-CoV-2 virus-like particles (VLPs) vaccine based on the Canarypox-virus vector (ALVAC-VLPs).
• To investigate the underlying immune mechanisms conferring protection against SARS-CoV-2 and its variants.

Main Methods:

• Development of ALVAC-VLPs vaccine using CRISPR/Cas9 technology.
• Immunization studies in mice and golden hamsters challenged with SARS-CoV-2 (wild-type and variants).
• Analysis of immune responses, including T and B cell activation, and mechanistic studies involving toll-like receptor 4 (TLR4).

Main Results:

• ALVAC-VLPs immunization induced specific T and B cell responses in mice, conferring resistance to lethal SARS-CoV-2 challenge.
• Golden hamsters vaccinated with ALVAC-VLPs showed protection against wild-type and multiple SARS-CoV-2 variants (Beta, Delta, Omicron BA.1, BA.2), evidenced by reduced disease severity and viral load.
• The vaccine's efficacy is linked to TLR4-mediated recruitment of dendritic cells, promoting T follicular helper (Tfh) cell differentiation, germinal center (GC) B cell proliferation, and plasma cell production.

Conclusions:

• The developed ALVAC-VLPs vaccine demonstrates significant immunogenicity and broad-spectrum efficacy against SARS-CoV-2 and its variants.
• The findings highlight the potential of ALVAC-VLPs as a safe and effective vaccine strategy for COVID-19.
• Understanding the TLR4-dependent immune pathways provides valuable insights for future vaccine development.