Attenuated Toxoplasma gondii ts-4 mutants engineered to express the Leishmania antigen KMP-11 elicit a specific immune response in BALB/c mice

In order to test recombinant Toxoplasma as adjuvant and live vaccine carrie r in the infectious disease model of murine experimental leishmaniasis, we engineered the attenuated, temperature-sensitive Toxoplasma gondii strain t s-4 to express the heterologous Leishmania antigen kinetoplastid membrane p rotein-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 ta chyzoites. Immunization of BALB/c mice with these stably transformed parasi tes elicited proliferative responses to both T gondii antigen and recombina nt KMP-11. When challenged with Leishmania major. we observed significant p rotection in animals that had been vaccinated with the KMP-11-expressing ts -4 mutants. The adjuvant attenuated only the onset of the Leishmania infect ion. but animals were ultimately not able to control the disease. Thus, our findings demonstrate that recombinant Toxoplasma has the potential to serv e 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. (C) 2001 Elsevier Science Ltd. All rights reserved.