Travoprost/Timolol Maleate

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.

The conventional inactivated tetanus toxin plays an instrumental role in preventing tetanus. Nevertheless, the challenges associated with its production process, the potential for adverse reactions, and reduced effectiveness in vulnerable populations such as neonates and the elderly rise the need for a novel tetanus toxin vaccine. Recombinant subunit vaccine offer a viable solution, and the tetanus toxin fragment C (TTFC) is emerging as a promising candidate. In this study, through spontaneous isopeptide bond formation we conjugated the recombinant TTFC to self-assembled mi3 nanoparticle, which derived from an optimized KDPG aldolase, and generated the TTFC-mi3 protein nanoparticle vaccine. We found that TTFC-mi3 is stable, uniform spherical nanoparticles. Comparing with the free TTFC alone, TTFC-mi3 enhances the uptake and subsequent activation of dendric cells (DCs). In addition, a single dose of adjuvant-free TTFC-mi3 elicited a more rapid and potent protective immunity in mice. Moreover, TTFC-mi3 is of favorable safety in vitro and in vivo. Our findings indicate that TTFC-mi3 is a rapid-response, non-aluminum-adjuvanted vaccine against tetanus.