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

The Journal of Infectious Diseases
A MuyombweBarbara Papadopoulou

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.

Citations

Sep 24, 2005·Infection and Immunity·Marie BretonBarbara Papadopoulou
May 31, 2014·PLoS Neglected Tropical Diseases·Noushin DavoudiW Robert McMaster
Sep 1, 2004·Expert Opinion on Biological Therapy·Jose M RequenaManuel Soto
Nov 10, 2011·Bioengineered Bugs·Sigrid C Roberts
May 28, 2011·International Immunopharmacology·Rajeev Nagill, Sukhbir Kaur
Mar 13, 2014·Expert Review of Vaccines·Shyam Sundar, Bhawana Singh
Mar 26, 2002·The Journal of Biological Chemistry·Nathalie BoucherBarbara Papadopoulou
Aug 29, 1998·The Journal of Biological Chemistry·E GhedinG Matlashewski

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