An in vivo comparison of bacillus Calmette-Guerin (BCG) and cytokine-secreting BCG vaccines

A recombinant bacillus Calmette-Guerin (BCG) vaccine has been developed, wh ich constitutively secretes interleukin (IL)-2. Groups of deer were immuniz ed with either normal BCG (Pasteur 1173 P2 strain) or recombinant BCG (rBCG /IL-2) and their immune responses were monitored over 3 months. Animals gai ned weight over this period and showed no signs of adverse reactions to eit her vaccine. Lymphocyte transformation responses did not differ significant ly between the two groups. No antibody that was specific for BCG was detect ed in any animal. Intradermal skin-test responses to BCG antigens showed th at the rBCG/IL-2 induced a smaller delayed-type hypersensitivity response t han the normal BCG. Cytokine transcription was determined by reverse transc ription-polymerase chain reaction (RT-PCR). While IL-2 and interferon-gamma (IFN-gamma) levels did not differ significantly between the two groups, th e level of IL-4 was found to be lower in the group given rBCG/IL-2, This re sulted in a strong interferon-gamma:IL-4 ratio, suggesting a skewing of the immune response towards a Type 1 response. The rate at which the vaccine w as eliminated from the host was the same regardless of whether BCG or rBCG was used. At autopsy (3 months after vaccination) 99.99% of the organisms h ad been eliminated. The small number of organisms isolated from the drainin g lymph node of animals given rBCG/IL-2 were grown in antibiotic-containing media. They were shown to still contain the shuttle plasmid and to secrete biologically active IL-2, indicating that the plasmid was stably maintaine d despite the host's immune response and in the absence of antibiotic selec tion.