HUMAN T-CELL RESPONSES INDUCED BY VACCINATION WITH MYCOBACTERIUM-BOVIS BACILLUS-CALMETTE-GUERIN

Many aspects of the widely used bacillus Calmette-Guerin (BCC) vaccine against tuberculosis are still the subject of controversy. There is a huge variation in efficacy from one clinical trial to another and no relationship between vaccine-induced skin test conversion and subseque nt protection. We have studied in vitro cell-mediated immune responses primed by BCG vaccination in 22 healthy Danish donors with different levels of in vitro purified protein derivative (PPD) reactivity before vaccination. The study demonstrated a markedly different development of reactivity to mycobacterial Ags depending on the prevaccination sen sitivity to PPD. Previously sensitized donors mounted a potent and hig hly accelerated recall response within the first week of BCC vaccinati on. Nonsensitized donors, in contrast, exhibited a gradually increasin g responsiveness to mycobacterial Ags, reaching maximal levels between day 56 and 365 postvaccination. The recognition of different classes of Ags were induced in a stepwise manner: culture filtrate Ags were re cognized 1 wk postvaccination followed by cell wall, membrane, and the cytosolic Ag fraction. The T cell response primed by BCG vaccination was characterized as a CD4 response with a Th1-like cytokine pattern a nd substantial levels of Ag-specific cytotoxicity. The specificity of the T cell response generated was broad and directed to a range of cul ture filtrate Ag fractions. The study shows that BCG vaccination of pr eviously nonsensitized donors can provide important data on potentiall y protective immune responses in humans and suggest a careful evaluati on of prevaccination sensitivity when investigating vaccine-induced im munity.