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-blind trial in Colombia. There were 4 vaccination groups: IM vaccine, IM placebo, 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 given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the 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 Leishmania-antigen lymphocyte proliferation indexes was observed after IM vaccine immunization, but not after IM placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma, but not IL-10 were observed 1 year after vaccination in the IM vaccine group compared to the IM placebo 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-based phase-III efficacy trial of the IM vaccine should be initiated.