Protection against Leishmania major challenge infection in mice vaccinated with live recombinant parasites expressing a cytotoxic gee

Abstract

A 'suicide' system based on thymidine kinase-ganciclovir combination was developed and tested in a Leishmania major experimental model. Susceptible BALB/c mice were infected with L. major expressing the thymidine kinase gene of herpes simplex virus type 1 and treated for 2 consecutive weeks with 7.5 mg/kg/day ganciclovir at different times from the initial infection. Ganciclovir treatment at varying times after infection had different effects on the outcome of disease. A complete inhibition of intracellular parasites was obtained in mice treated 1 or 4 days after infection, whereas ganciclovir administration 2 weeks later resulted in the control of infection only when the drug was provided. Variable levels of protection, from partial to total, against challenge infection with virulent L. major were observed, depending on the timing of ganciclovir treatment. The thymidine kinase-ganciclovir approach represents an excellent experimental model to control Leishmania infection and to evaluate the immunologic response of the host.