Oral Immunisation With Non-GMO Surface Displayed SARS-CoV-2 Spike Epitopes on Bacteria-Like Particles Provokes Robust...

Area of Science:

• Vaccinology
• Microbiology
• Immunology

Background:

• COVID-19, caused by SARS-CoV-2, is a significant global health threat.
• Existing vaccines have limitations; mucosal vaccines offer a promising alternative.
• Lactobacillus spp. are safe, food-grade bacteria suitable for vaccine development.

Purpose of the Study:

• To design and evaluate a non-GMO mucosal vaccine candidate against SARS-CoV-2.
• To assess the immunogenicity of surface-displayed SARS-CoV-2 spike S1 epitopes on Limosilactobacillus fermentum-derived bacteria-like particles (BLPs).
• To investigate the impact of oral immunization on the gut microbiome and host immune response.

Main Methods:

• Engineered Limosilactobacillus fermentum-derived BLPs to display SARS-CoV-2 spike S1 epitopes.
• Administered oral immunizations to C57BL/6 mice with PBS, BLPs, or epitope-displaying BLPs.
• Measured secretory IgA, systemic IgG, cytokine production (IFN-γ), and analyzed gut microbiome composition and metabolites.

Main Results:

• Mucosal immunization elicited robust secretory IgA and systemic IgG responses.
• A Th1-biased immune response was observed, indicated by a high IgG2a/IgG1 ratio and increased IFN-γ.
• Oral administration modulated the gut microbiome and increased beneficial butyrate production.

Conclusions:

• Limosilactobacillus fermentum-derived BLPs displaying SARS-CoV-2 spike S1 epitopes represent a promising mucosal vaccine strategy.
• This approach offers a potentially cost-effective, non-GMO alternative for COVID-19 prevention.
• The vaccine candidate effectively induces both local and systemic immunity while positively impacting gut health.