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Published on: September 19, 2016
Intranasal immunization with recombinant outer membrane protein A induces protective immune response against
Yan Li1,2,3, Xueping Tang2, Zunquan Zhao4
1No 307 Hospital of PLA of Anhui Medical University, Hefei, China.
Abstract:
Stenotrophomonas maltophilia (S. maltophilia), a multi-drug resistant opportunistic pathogen, is associated with nosocomial and community-acquired infections. Preventive and therapeutic strategies for such infections are greatly needed. In this study, sequence alignment analysis revealed that Outer membrane protein A (OmpA) was highly conserved among S. maltophilia strains but shared no significant similarity with human and mouse proteomes. In mice, intranasal immunization with S. maltophilia recombinant OmpA (rOmpA) without additional adjuvant induced sustained mucosal and systemic rOmpA-specific antibody responses. Treatment with rOmpA stimulated significantly higher levels of secretion of IFN-γ, IL-2, and IL-17A (All P<0.05) from the primary splenocytes isolated from rOmpA-immunized mice than from the primary splenocytes isolated from PBS-immunized mice. Furthermore, mice immunized with rOmpA showed significantly reduced bacterial burden in the lung and reduced levels of pro-inflammatory cytokines (TNF-α and IL-6) in bronchoalveolar lavage fluid (BALF) 24 hours after intranasal S. maltophilia infection, indicating that immunization with rOmpA may have protective effects against S. maltophilia challenge in mice. Our findings suggest that intranasal immunization with rOmpA may induce mucosal and systemic immune responses in mice, trigger Th1- and Th17-mediated cellular immune responses, and thus stimulate host immune defense against S. maltophilia infection. These results also demonstrate that intranasal vaccination may offer an alternative approach to current strategies since it induces a mucosal as well as a systemic immune response.
Insights
Intranasal vaccination with Outer membrane protein A (OmpA) from Stenotrophomonas maltophilia induced protective immunity in mice. This approach stimulated mucosal and systemic antibody responses, offering a potential new strategy against this resistant pathogen.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Stenotrophomonas maltophilia is a multi-drug resistant pathogen causing significant nosocomial and community infections.
- Effective preventive and therapeutic strategies against S. maltophilia are urgently needed.
- Outer membrane protein A (OmpA) is highly conserved in S. maltophilia and lacks homology with host proteins, making it a potential vaccine candidate.
Purpose of the Study:
- To investigate the immunogenicity and protective efficacy of intranasal immunization with recombinant OmpA (rOmpA) from S. maltophilia in a mouse model.
- To evaluate the induction of mucosal and systemic immune responses, cellular immunity, and protection against S. maltophilia challenge.
Main Methods:
- Sequence alignment analysis to assess OmpA conservation and host homology.
- Intranasal immunization of mice with S. maltophilia rOmpA without adjuvant.
- Measurement of rOmpA-specific antibody responses (mucosal and systemic).
- Assessment of splenocyte cytokine production (IFN-γ, IL-2, IL-17A) via ELISA.
- Quantification of bacterial burden and pro-inflammatory cytokines (TNF-α, IL-6) in lung and bronchoalveolar lavage fluid (BALF) post-challenge.
Main Results:
- Intranasal rOmpA immunization induced sustained mucosal and systemic rOmpA-specific antibody responses.
- rOmpA immunization significantly increased IFN-γ, IL-2, and IL-17A secretion from splenocytes.
- Immunized mice exhibited reduced lung bacterial burden and lower levels of TNF-α and IL-6 in BALF after S. maltophilia challenge.
- The study demonstrated protective effects of rOmpA immunization against S. maltophilia infection.
Conclusions:
- Intranasal immunization with S. maltophilia rOmpA effectively induces protective immunity in mice.
- This vaccination strategy elicits both mucosal and systemic immune responses, including Th1 and Th17-mediated cellular immunity.
- Intranasal vaccination with rOmpA presents a promising alternative approach for preventing and treating S. maltophilia infections.
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