Immune response measured in human volunteers vaccinated with autoclavedLeishmania majorvaccine mixed with low dose of BCG

Abstract

The immune responses induced against Leishmania antigens in volunteers who were vaccinated in a double-blind, randomized field efficacy trial of a preparation of autoclaved Leishmania major (ALM) mixed with a low dose of Bacille Calmette-Guerin vaccine (BCG) who developed either a cutaneous leishmaniasis (CL) lesion due to exposure to infected sandfly bite(s) or did not develop a lesion during the course of the trial were studied and compared with those of non-vaccinated controls. Blood samples were also assayed from different groups including volunteers with history of CL and volunteers with previous positive or negative leishmanin skin test (LST) without a history of CL. The vaccinated volunteers had received a single dose of either ALM mixed with a low dose of BCG or the same dose of BCG alone. The LST and in vitro proliferative response (stimulation index, SI), interferon gamma (IFN-gamma) production and, in a few cases, interleukin (IL)-4 production of peripheral blood mononuclear cells to soluble Leishmania antigens were measured. The results indicated that volunteers who developed CL in the vaccine arm showed a slightly higher SI than cases who received BCG alone. Volunteers with history of CL and volunteers with positive LST demonstrated the strongest proliferation indices and IFN-gamma production. The data suggest that a single dose of ALM + BCG induces a weak Th1 response in vaccinated volunteers that is far lower than that in volunteers with prior subclinical infection or volunteers with history of CL, who are presumed to be immune.