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

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

Author information

1
TherapyX Inc., Buffalo, New York, USA.
2
Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
3
Department of Pediatrics, Digestive Diseases and Nutrition Center, University at Buffalo, Buffalo, New York, USA.
4
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
5
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, USA.
6
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
7
Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.

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.

PMID:
28272393
PMCID:
PMC5591041
DOI:
10.1038/mi.2017.11
[Indexed for MEDLINE]
Free PMC Article

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