IMMUNE-RESPONSE IN HEALTHY-VOLUNTEERS VACCINATED WITH KILLED LEISHMANIAL PROMASTIGOTES PLUS BCG .1. SKIN-TEST REACTIVITY, T-CELL PROLIFERATION AND INTERFERON-GAMMA PRODUCTION

This study reports the results of a vaccine trial established to study the cellular immune responses in vivo (skin-test reactivity) and in v itro (T-cell proliferation and interferon-gamma production) to both le ishmanial and mycobacterial antigens following vaccination of healthy volunteers from a leishmaniasis-endemic area with killed leishmanial p romastigotes, with or without BCG (Bacille Calmette-Guerin). Skin test s were performed using purified protein derivative of tuberculin (PPD) and leishmanial antigen in 692 volunteers, and 208 doubly negative su bjects (less than or equal to 7 mm induration) were selected to partic ipate in the trial. The study subjects were divided into four vaccine groups: (A) killed promastigotes plus BCG, (B) BCG alone, (C) killed p romastigotes alone, and(D) placebo. Three vaccine doses were administe red at 6-10-week intervals. The skin-test responses to PPD and leishma nial antigen were reassessed at 4-6- and 12-18-month follow-ups. The r esults of this trial demonstrated that the combined vaccine, i.e. kill ed promastigotes of Leishmania plus BCG, results in the stimulation of an immune response to both leishmanial and mycobacterial antigens in a high percentage of vaccines (>85%), manifested either by skin-test c onversion, lymphocyte proliferation and/or interferon-gamma production . This was evident after the first dose of vaccine for lymphocyte prol iferation and interferon-gamma production and was maintained for a yea r after the three doses of vaccine. Group B (which received BCG alone) , responded as well as group A to PPD but not as well to leishmanial a ntigen. The reverse was true for group C which received promastigotes alone. Group A attained a 38% leishmanin skin-test conversion at the 4 -6-month follow-up, which was associated with double PPD/leishmanial a ntigen responder status. In contrast, a 35% skin-test conversion was f ound at the 12-18-month follow-up in group C (promastigotes alone), bu t this was not associated with responses to PPD. A significant percent age of conversion was observed in the placebo group at the 12-18-month follow-up, both to PPD (58%) and leishmanial (21%) antigens, which su ggests either environmental exposure to mycobacterial or leishmanial a ntigens during the vaccine trial or, more probably, a response to the repeated leishmanial skin tests. Further studies are required to deter mine whether the presence of proliferative and/or interferon-gamma res ponses in the absence of a skin-test response are sufficient indicator s of potential vaccine success.