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 benefits 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 provide effective immune protection through a Th2-polarized response, highlighting the potential of CBVs as a versatile tool for developing new-generation vaccines.

Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is considered a toxemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F(ab’)2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS. A single-center, randomized, Phase 1, single-blind, placebo-controlled clinical trial to evaluate INM004 safety, tolerance, and pharmacokinetics (PK) in healthy adult volunteers, was conducted; In Stage I, eight subjects were divided in two cohorts (n=4) to receive a single INM004 dose of 2 or 4 mg.kg-1, or placebo (INM004:placebo rate 3:1). In Stage II six subjects received either three INM004 doses of 4 mg.kg-1 repeated every 24 h, or placebo (INM004:placebo rate of 5:1). Hospital discharged was 24 hours after the last infusion. INM004 was quantified by ELISA in serum samples obtained at predefined times. Safety and tolerability were assessed in both Stages by monitoring adverse events (AEs), laboratory test values, and vital signs. Eight subjects (57.1%) experienced treatment-emergent AEs (TEAEs), that resolved within 24 hours without requiring changes in treatment or additional intervention. No serious AEs were reported. Most TEAEs were of mild or moderate intensity, and four were possibly drug-related. Peak concentrations (Cmax) of INM004 were 45.1 µg.mL-1 and 77.7 µg.mL-1 for different doses, within two hours after infusion. The serum concentration declined in a biphasic manner (t1/2 range 30.7-52.9 hours). Systemic exposures showed accumulation in the repeated dose regimen (Cmax Day1 85.7 vs.149 µg.mL-1 Day3). These results supporting progression into the phase 2 trial in children with HUS