title: Experimental Leishmania major infection suppresses HIV-1 DNA vaccine induced cellular immune response.
abstract: The AIDS epidemic in the developing world represents a major global crisis and an effective vaccine is imperative. However, many parasites are common in developing countries and can result in a state of chronic immune activation that is polarized towards a Th2 profile and which can potentially impair responses to vaccines or other infectious challenges. In this study we demonstrate that experimental Leishmania major infection of BALB/c mice inhibits responses to a DNA-based HIV-1 gag vaccine. L. major infection in BALB/c results in a polarized Th2 immune response. In this study naïve BALB/c mice immunized with the HIV-1 gag DNA vaccine mounted a cellular immune response against the vaccine antigen, HIV-1 gag. CD8+ T lymphocytes were able to respond in vitro to HIV-1 gag stimulation and secrete interferon (IFN)-gamma. However, L. major-infected, vaccinated BALB/c mice had a significantly reduced number of IFN-gamma-producing CD8+ T cells following in vitro stimulation with gag antigen. These data suggest that parasitic infection, which results in a Th2 profile, reduces the efficacy of DNA vaccines that are designed to induce antiviral CD8+ T cell responses.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Robinson
authors.forename: Robin
authors.initials: R
authors.lastname: Nelson
authors.forename: David
authors.initials: D
authors.lastname: Artis
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015750:Genes, gag; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology
chemical_list: D016915:AIDS Vaccines; D000953:Antigens, Protozoan; D019444:Vaccines, DNA