IMMUNE-RESPONSE IN HEALTHY-VOLUNTEERS VACCINATED WITH BCG PLUS KILLEDLEISHMANIAL PROMASTIGOTES - ANTIBODY-RESPONSES TO MYCOBACTERIAL AND LEISHMANIAL ANTIGENS

Antibody (IgG) responses to mycobacterial (BCG, PPD; Mycobacterium lep rae soluble antigen, MLSA) and leishmanial (Leishmania mexicana LV4) a ntigens were measured in 208 initially PPD and leishmanin skin-test ne gative volunteers divided into four vaccine groups as follows: 68 rece ived BCG plus killed promastigotes (group A), 47 received BCG alone (g roup B), 47 received killed promastigotes alone (group C), and 46 for med the diluent control (placebo, group D). Three vaccine doses were a dministered at 8-12 week intervals. Vaccinees were bled immediately pr ior to each vaccination, and again at 3- and 12-month follow-lip. Skin tests were performed prevaccination, and again at the 3- and 12-month follow-up. Anti-BCG, anti-PPD and anti-MLSA IgG levels increased sign ificantly in groups A and B receiving BCG. The presence of leishmanial antigen (with BCG) in the inoculum suppressed the IgG response to Myc obacterium tuberculosis/Mycobacterium bovis-related (PPD and BCG), but not M. leprae-related (MLSA)-related antigens. A small but significan t increase (relative to prevaccination level) in response to MLSA, but not to BCG or PPD was observed in the non-BCG-vaccinated groups. The background level of response to mycobacterial and leishmanial antigens was higher in the Venezuelan vaccinees than in non-endemic (British) volunteers. Responses to leishmanial antigen were not enhanced in the two vaccine groups receiving killed promastigotes (with/without BCG) c ompared with the BCG alone and placebo groups. Instead, all vaccine gr oups showed a pattern of response consistent with either (i) a respons e to the skin-test antigen or, more likely, (ii) seasonal endemic expo sure to leishmanial antigen. Interestingly, this endemic response to l eismanial antigen was enhanced in the vaccine groups receiving BCG, de spite the fact that group B received no leishmanial antigen in the vac cine inoculum. When prevaccination IgG levels (mean+3 standard deviati ons) were used to determine a negative cut-off, a low percentage (< 38 %) of vaccinees converted to responder status for either anti-mycobact erial or anti-leishmanial responses, and those who did would be classi fied as 'low-responder' status compared with titres observed in severe forms of disease. Hence, although there was evidence for a background endemic response to both leishmanial and mycobacterial antigens, ther e was no evidence that vaccination per se led to a potentially disease exacerbatory level of TH2-associated antibody response especially wit h respect to the anti-leishmanial response. Taken together with our ea rlier report that a high proportion of vaccinees, particularly in the BCG plus killed promastigotes group (> 90%), converted for T-cell resp onder phenotypes (skin test; proliferative response; interferon-gamma production) to leishmanial antigens, these results indicate that this vaccine is potentially protective for the majority of vaccinees. The r esults of this small trial thus provide a level of confidence in exten ding the protocol to test the efficacy of BCG plus whole killed parasi te vaccines in preventing disease.