Immune response in healthy volunteers vaccinated with killed leishmanial promastigotes plus BCG. I: 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 vitro (T-cell proliferation and interferon-gamma production) to both leishmanial and mycobacterial antigens following vaccination of healthy volunteers from a leishmaniasis-endemic area with killed leishmanial promastigotes, with or without BCG (Bacille Calmètte-Guerin). Skin tests were performed using purified protein derivative of tuberculin (PPD) and leishmanial antigen in 692 volunteers, and 208 doubly negative subjects (< or = 7 mm induration) were selected to participate in the trial. The study subjects were divided into four vaccine groups: (A) killed promastigotes plus BCG, (B) BCG alone, (C) killed promastigotes alone, and (D) placebo. Three vaccine doses were administered at 6-10-week intervals. The skin-test responses to PPD and leishmanial antigen were reassessed at 4-6- and 12-18-month follow-ups. The results of this trial demonstrated that the combined vaccine, i.e. killed promastigotes of Leishmania plus BCG, results in the stimulation of an immune response to both leishmania and mycobacterial antigens in a high percentage of vaccines (> 85%), manifested either by skin-test conversion, lymphocyte proliferation and/or interferon-gamma production. This was evident after the first dose of vaccine for lymphocyte proliferation and interferon-gamma production and was maintained for a year 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 antigen. 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 antigen responder status. In contrast, a 35% skin-test conversion was found at the 12-18-month follow-up in group C (promastigotes alone), but this was not associated with responses to PPD. A significant percentage of conversion was observed in the placebo group at the 12-18-month follow-up, both to PPD (58%) and leishmanial (21%) antigens, which suggests either environmental exposure to mycobacterial or leishmanial antigens during the vaccine trial or, more probably, a response to the repeated leishmanial skin tests. Further studies are required to determine whether the presence of proliferative and/or interferon-gamma responses in the absence of a skin-test response are sufficient indicators of potential vaccine success.
Instituto de Biomedicina, Facultad de Medicina, Universidad Central de Venezuela, Caracas.
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Castés
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Blackwell
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Trujillo
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Formica
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Cabrera
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Zorrilla
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Rodas
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Castellanos
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Convit
D000293:Adolescent; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis*; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology
D016052:Protozoan Vaccines; D007371:Interferon-gamma