Coated Bacterial Vaccine: A New Approach for Antigen Display on Bacterial Surface

Abstract

Bacterial vaccines using recombinant antigens displayed on the bacterial surface represent a major advancement in vaccine development. This approach leverages bacteria's natural ability to induce immune responses while improving vaccine targeting and efficacy. Existing platforms, such as live bacterial vaccines, inactivated bacterial vaccines, and bacterial-like particles (BLPs), face challenges like genetic modifications, antigen dilution, and degradation. To address these limitations, a novel system called coated bacterial vaccine (CBV) is proposed, combining the properties of inactivated bacterial vaccines and BLPs technology. The recombinant antigen is fused to the carboxy-terminal cell wall-binding domain of the Lactobacillus SlpA protein (dSLPA) and anchored in vitro on chemically inactivated Gram-positive bacteria. To validate this system, CBVs were created using inactivated B. subtilis 15245 and the TTFC antigen, a fragment of tetanus toxin (TeTx) fused with dSLPA. CBVs were used to immunize BALB/c mice, and anti-TTFC IgG antibodies were measured. Mice were then challenged with TeTx to assess the protective effects of CBVs. Results showed a 100% survival rate in vaccinated mice after TeTx challenge, driven by a robust anti-TTFC IgG response, particularly elevated IgG1 levels. Additionally, macrophage stimulation assays showed increased mRNA levels for IL-1β, IL-6, and IL-10, along with significant IL-6 secretion. These findings demonstrate that CBVs based on B. subtilis can promote active immune protection against TeTx challenge, likely mediated by a Th2-polarized immune response, highlighting the potential of CBVs as a versatile tool for developing new-generation vaccines.