title: Immunotherapeutic approaches to enhance protective immunity against Candida vaginitis.
abstract: Protective host defense mechanisms against vaginal Candida infections are poorly understood. While cell-mediated immunity (CMI) is the predominant host-defense mechanism against most mucosal Candida infections, no protective role for systemic or local Candida-specific CMI or antibodies has been identified against vaginal candidiasis. Rather, evidence exists for immunoregulation in vaginal tissue, which may inhibit a more profound protective Th1-type response. This study evaluated immunotherapy and gene therapy approaches in the murine model to potentially overcome immunoregulation and promote enhanced protection against vaginal candidiasis. In the first set of studies, the intravaginal and systemic administration of Thl-type cytokines and anti-IL-10 and anti-TGF-beta antibodies failed to enhance protection against a vaginal Candida infection. In a second set of studies, the novel intravaginal administration of Adenoviruses encoding Th1-type cytokines (IFN-gamma and IL-12) and the chemokine, MCP-1, showed substantial, but transient (24 h) expression of each in vaginal tissue and draining lymph nodes, even with a second administration. Unfortunately, treatment with these Adenoviral vectors did not enhance protection against experimental vaginitis. Construction of a new vector encoding IFN-gamma with a stronger promoter produced substantial IFN-gamma in vitro, but lower amounts in vivo and no extended expression. Taken together, while gene therapy can be used to induce cytokine expression in vaginal tissue, there appear to be strong regulatory mechanisms that additional manipulations or alternative approaches will have to overcome if protection against vaginitis is to be enhanced.
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center New Orleans, LA 70112, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wozniak
authors.forename: Glen
authors.initials: G
authors.lastname: Palmer
authors.forename: Robert
authors.initials: R
authors.lastname: Kutner
authors.forename: Paul L
authors.initials: PL
authors.lastname: Fidel
mesh_terms: D000818:Animals; D002175:Candida / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology / Q000628:therapy*; D002181:Candidiasis, Vulvovaginal / Q000276:immunology* / Q000628:therapy; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008808:Mice, Inbred CBA; D014627:Vaginitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*
chemical_list: D016207:Cytokines; D007371:Interferon-gamma