Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model.

Publication Type:

Journal Article

Source:

Mucosal immunology, Volume 10, Issue 6, p.1594-1608 (2017)

Keywords:

Animals, Antibodies, Viral, Bacterial Load, Bacterial Vaccines, Cells, Cultured, Disease Models, Animal, Extracellular Vesicles, Female, Gonorrhea, Humans, Immunization, interferon-gamma, Interleukin-12, Lymphocyte Activation, MICE, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Neisseria gonorrhoeae, Peptide Elongation Factor Tu, Porins, Proteomics Core Facility, Th1 Cells

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.