title: Attenuated Toxoplasma gondii ts-4 mutants engineered to express the Leishmania antigen KMP-11 elicit a specific immune response in BALB/c mice.
abstract: In order to test recombinant Toxoplasma as adjuvant and live vaccine carrier in the infectious disease model of murine experimental leishmaniasis, we engineered the attenuated, temperature-sensitive Toxoplasma gondii strain ts-4 to express the heterologous Leishmania antigen kinetoplastid membrane protein-11 (KMP-11). Transgenic ts-4 clones were obtained which express KMP-11 as cytoplasmatic protein or target it to the secretory pathway of the tachyzoites. Immunization of BALB/c mice with these stably transformed parasites elicited proliferative responses to both T. gondii antigen and recombinant KMP-11. When challenged with Leishmania major, we observed significant protection in animals that had been vaccinated with the KMP-11-expressing ts-4 mutants. The adjuvant attenuated only the onset of the Leishmania infection, but animals were ultimately not able to control the disease. Thus, our findings demonstrate that recombinant Toxoplasma has the potential to serve as an efficient vaccine carrier for cutaneous leishmaniasis. Furthermore, they establish a protective role for the antigen KMP-11 when given in such a vaccine formulation.
authors.affiliation: Programa de Estudio y Control de Enfermedades Tropicales, Universidad de Antioquia, A.A. 1225 Medellín, Colombia.
authors.forename: J R
authors.initials: JR
authors.lastname: Ramírez
authors.forename: K
authors.initials: K
authors.lastname: Gilchrist
authors.forename: S
authors.initials: S
authors.lastname: Robledo
authors.forename: J C
authors.initials: JC
authors.lastname: Sepúlveda
authors.forename: H
authors.initials: H
authors.lastname: Moll
authors.forename: D
authors.initials: D
authors.lastname: Soldati
authors.forename: C
authors.initials: C
authors.lastname: Berberich
mesh_terms: D000818:Animals; D005260:Female; D007891:Leishmania / Q000276:immunology*; D007896:Leishmaniasis / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014122:Toxoplasma / Q000235:genetics*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C090009:kinetoplastid membrane protein 11, Leishmania donovani