title: Reduced pathology following infection with transgenic Leishmania major expressing murine CD40 ligand.
abstract: Leishmanization is the inoculation of live Leishmania into the host to vaccinate against subsequent infections. This approach has been largely discontinued due to safety concerns. We have previously shown that combining CD40 ligand (CD40L) with Leishmania antigen preferentially induces a type 1 immune response and provides some protection to vaccinated mice (G. Chen, P. A. Darrah, and D. M. Mosser, Infect. Immun. 69:3255-3263, 2001). In the present study, we developed transgenic L. major organisms which express and secrete the extracellular portion of CD40L (L. major CD40LE). We hypothesized that these organisms would be less virulent but more immunogenic than wild-type organisms and therefore be more effective at leishmanization. Transgenic parasites expressing CD40L mRNA and protein were developed. BALB/c mice infected with these parasites developed significantly smaller lesions containing fewer parasites than animals infected with wild-type organisms. Infection of resistant C57BL/6 mice with low doses of transgenic parasites induced a significant amount of protection against subsequent high-dose infection with wild-type organisms. These results demonstrate that transgenic organisms expressing CD40L are less virulent than wild-type organisms while retaining full immunogenicity.
authors.affiliation: University of Maryland, 1103 Microbiology Building (Building 231), College Park, MD 20742, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Field
authors.forename: Sagie
authors.initials: S
authors.lastname: Wagage
authors.forename: Sean M
authors.initials: SM
authors.lastname: Conrad
authors.forename: David M
authors.initials: DM
authors.lastname: Mosser
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000276:immunology*; D018320:Leishmania major / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified; D016052:Protozoan Vaccines / Q000276:immunology*; D014611:Vaccination
chemical_list: D019013:CD40 Antigens; D016052:Protozoan Vaccines; D023201:CD40 Ligand