Safety and immunogenicity of a killed Leishmania (L.) amazonensis vaccine against cutaneous leishmaniasis in Colombia: a randomized controlled trial

The safety and immunogenicity of an intramuscular (IM) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-bli nd trial in Colombia. There were 4 vaccination groups: IM vaccine, IM place bo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were give n with a 20-day interval between injections, and adverse events were monito red at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced ad verse reactions resulted in cancellation of the third vaccine administratio n in the ID groups. Antibody titres did not differ significantly between th e groups. Montenegro skin-test conversion was achieved by 86.4 % and 90% of the IM vaccine group and by 25% and 5% of the IM placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Lei shmania-antigen lymphocyte proliferation indexes was observed after IM vacc ine immunization, but not after IM placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma, but not IL-10 were obs erved 1 year after vaccination in the IM vaccine group compared to the IM p lacebo group. The good safety profile and evidence of Th1 immune reactions due to LM vaccination in this phase-I/II study suggest that a population-ba sed phase-III efficacy trial of the IM vaccine should be initiated.