Immunization with Inactivated <i>Bacillus subtilis</i> Spores Expressing TonB-Dependent Receptor (TBDR) Protects Against Multidrug-Resistant <i>Acinetobacter baumannii</i> Infection
Background/Objectives: The emergence of multidrug-resistant <i>Acinetobacter baumannii</i> (MDR <i>A. baumannii</i>) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live <i>Bacillus s...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/6/616 |
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| Summary: | Background/Objectives: The emergence of multidrug-resistant <i>Acinetobacter baumannii</i> (MDR <i>A. baumannii</i>) as a leading cause of fatal hospital-acquired infections underscores the urgent need for effective vaccines. While oral vaccines using live <i>Bacillus subtilis</i> spores expressing <i>A. baumannii</i> TonB-dependent receptor (TBDR) show promise, biosafety concerns regarding recombinant spore persistence necessitate alternative strategies. Here, we evaluated chemically inactivated <i>B. subtilis</i> 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 <i>A. baumannii</i> 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 <i>B. subtilis</i> spores expressing TBDR are a safe, orally administrable vaccine platform that elicits protective immunity against MDR <i>A. baumannii</i>. By addressing biosafety concerns associated with live spores while maintaining efficacy, this approach represents a critical advance toward preventing high-risk nosocomial infections. |
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| ISSN: | 2076-393X |