title: Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model.
abstract: Female mice were immunized intravaginally with gonococcal outer membrane vesicles (OMVs) plus microencapsulated interleukin-12 (IL-12), and challenged using an established model of genital infection with Neisseria gonorrhoeae. Whereas sham-immunized and control animals cleared the infection in 10-13 days, those immunized with OMV plus IL-12 cleared infection with homologous gonococcal strains in 6-9 days. Significant protection was also seen after challenge with antigenically distinct strains of N. gonorrhoeae, and protective anamnestic immunity persisted for at least 6 months after immunization. Serum and vaginal immunoglobulin G (IgG) and IgA antibodies were generated against antigens expressed by homologous and heterologous strains. Iliac lymph node CD4+T cells secreted interferon-γ (IFNγ), but not IL-4, in response to immunization, and produced IL-17 in response to challenge regardless of immunization. Antigens recognized by immunized mouse serum included several shared between gonococcal strains, including two identified by immunoproteomics approaches as elongation factor-Tu (EF-Tu) and PotF3. Experiments with immunodeficient mice showed that protective immunity depended upon IFNγ and B cells, presumably to generate antibodies. The results demonstrated that immunity to gonococcal infection can be induced by immunization with a nonliving gonococcal antigen, and suggest that efforts to develop a human vaccine should focus on strategies to generate type 1 T helper cell (Th1)-driven immune responses in the genital tract.
authors.affiliation: TherapyX Inc., Buffalo, New York, USA.|Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: TherapyX Inc., Buffalo, New York, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Hammer
authors.affiliation: Department of Pediatrics, Digestive Diseases and Nutrition Center, University at Buffalo, Buffalo, New York, USA.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Hobbs
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Zielke
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Sikora
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Jerse
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
authors.forename: N K
authors.initials: NK
authors.lastname: Egilmez
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Russell
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006069:Gonorrhea / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D010444:Peptide Elongation Factor Tu / Q000276:immunology; D018272:Porins / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D001428:Bacterial Vaccines; D018272:Porins; C057699:porin protein, Neisseria; D018664:Interleukin-12; D007371:Interferon-gamma; D010444:Peptide Elongation Factor Tu