Vaccination of mice with a combination of BCG and killed Leishmania promastigotes reduces acute Trypanosoma cruzi infection by promoting an IFN-gammaresponse

The combination of BCG with killed Leishmania promastigotes, demonstrated t o be efficient in the cure of patients suffering American cutaneous leishma niasis and in the induction of a long-term immune response in healthy vacci nated volunteers, was tested in BALB/c mice infected with Trypanosoma cruzi , in comparison to BCG or Leishmania alone, and a vehicle (PBS) control. BC G-Leishmania vaccination, applied intra-peritoneally 10 and 3 days before T . cruzi trypomastigote inoculation, prolonged the survival, and reduced blo od parasitaemia of infected animals. Proliferation studies indicated that s plenocytes of mice vaccinated with BCG-Leishmania and harvested in the acut e phase of T. cruzi infection displayed stimulation indices higher than cel ls from PBS-treated mice when stimulated with PHA mitogen, PPD, Leishmania or T. cruzi antigens. Injections of a monoclonal antibody able to neutralis e IFN-gamma into BCG-Leishmania vaccinated mice increased parasitaemia to l evels similar to those of control animals (treated with PBS) and reversed t he beneficial effect of vaccination on the proliferative response to T. cru zi antigen. These results show that vaccination of mice with BCG plus kille d Leishmania promastigotes delayed acute T. cruzi infection, stimulated a T -cell response to T. cruzi antigen and promoted IFN-gamma production. (C) 1 999 Elsevier Science Ltd. All rights reserved.