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Immunization with Inactivated Bacillus subtilis Spores Expressing TonB-Dependent Receptor (TBDR) Protects Against
Amalia A Saperi1, Atiqah Hazan1, Nurfatihah Zulkifli1
1Tropical Infectious Diseases Research and Education Centre (TIDREC), University Malaya, Kuala Lumpur 50603, Malaysia.
Background/Objectives:
The emergence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live Bacillus subtilis spores expressing A. baumannii TonB-dependent receptor (TBDR) show promise, biosafety concerns regarding recombinant spore persistence necessitate alternative strategies. Here, we evaluated chemically inactivated B. subtilis spores displaying TBDR as a safer yet immunogenic vaccine candidate.
Methods:
Recombinant spores were inactivated using iron-ethanol sporicidal solution and administered to BALB/c mice (8-12 weeks old) to assess safety and immunogenicity. Toxicity was evaluated through clinical monitoring, serum biochemistry, and histopathology. Immune responses were characterized by T/B cell activation, IgG/IgA titers, and mucosal sIgA levels. Protective efficacy was determined by challenging immunized mice with MDR A. baumannii Ab35 and quantifying bacterial loads and examining tissue pathology.
Results:
The inactivated spores exhibited an excellent safety profile, with no adverse effects on clinical parameters, organ function, or tissue integrity. Immunization induced robust systemic and mucosal immunity, evidenced by elevated CD4+/CD8+ T cells, B cells, and antigen-specific IgG/IgA in serum and mucosal secretions. Following the challenge, vaccinated mice showed significantly reduced pulmonary bacterial burdens (>90% reduction), and preserved lung and spleen architecture compared to controls, which developed severe inflammation and tissue damage.
Conclusions:
These findings demonstrate that inactivated B. subtilis spores expressing TBDR are a safe, orally administrable vaccine platform that elicits protective immunity against MDR A. baumannii. By addressing biosafety concerns associated with live spores while maintaining efficacy, this approach represents a critical advance toward preventing high-risk nosocomial infections.
Insights
Chemically inactivated Bacillus subtilis spores displaying Acinetobacter baumannii TBDR offer a safe oral vaccine. This approach induces protective immunity against multidrug-resistant Acinetobacter baumannii, addressing biosafety concerns for preventing hospital infections.
Area of Science:
- Microbiology
- Vaccinology
- Immunology
Background:
- Multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) is a major cause of fatal hospital-acquired infections.
- Live Bacillus subtilis spores expressing A. baumannii TBDR show promise as oral vaccines but raise biosafety concerns.
- Safer alternatives are needed to develop effective vaccines against MDR A. baumannii.
Purpose of the Study:
- To evaluate chemically inactivated B. subtilis spores displaying TBDR as a safe and immunogenic vaccine candidate.
- To assess the safety, immunogenicity, and protective efficacy of this inactivated spore vaccine platform.
Main Methods:
- Recombinant B. subtilis spores were inactivated using an iron-ethanol sporicidal solution.
- Safety was assessed via clinical monitoring, serum biochemistry, and histopathology in mice.
- Immunogenicity was evaluated by measuring T/B cell activation, IgG/IgA titers, and mucosal sIgA.
- Protective efficacy was determined by challenging immunized mice with MDR A. baumannii and quantifying bacterial loads.
Main Results:
- Inactivated spores demonstrated an excellent safety profile with no observed toxicity.
- Immunization induced robust systemic and mucosal immune responses, including elevated antigen-specific IgG/IgA.
- Vaccinated mice exhibited significantly reduced pulmonary bacterial burdens (>90%) and preserved tissue architecture after challenge.
Conclusions:
- Chemically inactivated B. subtilis spores displaying TBDR represent a safe, orally administrable vaccine platform.
- This approach elicits protective immunity against MDR A. baumannii infections.
- It offers a critical advance in preventing high-risk nosocomial infections by addressing biosafety concerns.
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