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

Mucosal Immunol. 2017 Nov;10(6):1594-1608. doi: 10.1038/mi.2017.11. Epub 2017 Mar 1.

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.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Bacterial Load
  • Bacterial Vaccines / immunology*
  • Cells, Cultured
  • Disease Models, Animal
  • Extracellular Vesicles / immunology
  • Extracellular Vesicles / metabolism*
  • Female
  • Gonorrhea / immunology*
  • Humans
  • Immunization
  • Interferon-gamma / metabolism
  • Interleukin-12 / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neisseria gonorrhoeae / immunology*
  • Peptide Elongation Factor Tu / immunology
  • Porins / immunology
  • Porins / metabolism*
  • Th1 Cells / immunology*

Substances

  • Antibodies, Viral
  • Bacterial Vaccines
  • Porins
  • porin protein, Neisseria
  • Interleukin-12
  • Interferon-gamma
  • Peptide Elongation Factor Tu