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Intranasal immunization with recombinant outer membrane protein A induces protective immune response against Stenotrophomonas maltophilia infection.

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.
AuthorsYan Li, Xueping Tang, Zunquan Zhao, Hui Wang, Xin Wang, Xueyi Shang, Peng Liu, Zhihua Kou, Yongqiang Jiang, Yan Li
JournalPloS one (PLoS One) Vol. 14 Issue 4 Pg. e0214596 ( 2019) ISSN: 1932-6203 [Electronic] United States
PMID30934008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Interleukin-6
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • OMPA outer membrane proteins
Topics
  • Adjuvants, Immunologic
  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial (immunology)
  • Antibody Formation
  • Bacterial Outer Membrane Proteins (administration & dosage, immunology)
  • Bacterial Vaccines (administration & dosage, immunology)
  • Bronchoalveolar Lavage Fluid
  • Computational Biology
  • Female
  • Gram-Negative Bacterial Infections (drug therapy, prevention & control)
  • Interleukin-6 (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins (administration & dosage, immunology)
  • Sequence Analysis, DNA
  • Spleen (immunology)
  • Stenotrophomonas maltophilia
  • Th1 Cells (cytology)
  • Th17 Cells (cytology)
  • Tumor Necrosis Factor-alpha (metabolism)

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