Enhancement of adaptive immunity to Neisseria gonorrhoeae by local intravaginal administration of microencapsulated interleukin 12.
Gonorrhea remains one of the most frequent infectious diseases, and Neisseria gonorrhoeae is emerging as resistant to most available antibiotics, yet it does not induce a state of specific protective immunity against reinfection. Our recent studies have demonstrated that N. gonorrhoeae proactively suppresses host T-helper (Th) 1/Th2-mediated adaptive immune responses, which can be manipulated to generate protective immunity. Here we show that intravaginally administered interleukin 12 (IL-12) encapsulated in sustained-release polymer microspheres significantly enhanced both Th1 and humoral immune responses in a mouse model of genital gonococcal infection. Treatment of mice with IL-12 microspheres during gonococcal challenge led to faster clearance of infection and induced resistance to reinfection, with the generation of gonococcus-specific circulating immunoglobulin G and vaginal immunoglobulin A and G antibodies. These results suggest that local administration of microencapsulated IL-12 can serve as a novel therapeutic and prophylactic strategy against gonorrhea, with implications for the development of an effective vaccine.
Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, New York.
Yingru
Y
Liu
Nejat K
NK
Egilmez
Michael W
MW
Russell
D056704:Adaptive Immunity; D000282:Administration, Intravaginal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004339:Drug Compounding; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006069:Gonorrhea / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D000907:Antibodies, Bacterial; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12
IL-12; Neisseria gonorrhoeae; cytokine therapy; immunity; microencapsulation