A randomized double-blind placebo-controlled trial to evaluate the immunogenicity of a candidate vaccine against American tegumentary leishmaniasis

This study was aimed at evaluating the immunogenicity of a vaccine composed of killed Leishmania amazonensis promastigotes using several different pro tocols in a randomized, double-blind and controlled trial design in order t o select one of them for further efficacy trials. One hundred and fourteen leishmanin skin test (LST)-negative healthy volunteers were allocated into eight groups that received either two or three deep intramuscular injection s of vaccine at doses of 180, 360 and 540 mug or similar injections of plac ebo. Cell-mediated immune responses were evaluated before and after vaccina tion by means of LST as well as Proliferative responses and cytokine produc tion in Leishmania antigen-stimulated peripheral blood mononuclear cell cul tures. The majority of the subjects who actually received vaccine converted to positive LST (89.5%). On the other hand, none of the subjects who recei ved placebo converted to positive LST. Proliferative responses and producti on of interferon-gamma and interleukin-2 were significantly higher after va ccination than before vaccination in all groups, including those that recei ved placebo. The dose of 360 mug provided the highest LST conversion rate ( 100%), as well as the greatest increase in interferon-gamma and interleukin -2 production after vaccination. (C) 2001 Elsevier Science B.V. All rights reserved.