EFFECTIVE IMMUNIZATION AGAINST CUTANEOUS LEISHMANIASIS WITH RECOMBINANT BACILLE CALMETTE-GUERIN EXPRESSING THE LEISHMANIA SURFACE PROTEINASE GP63

Leishmania parasites cause a spectrum of diseases that afflict the pop ulations of 86 countries in the world. The parasites can survive withi n the lysosomal compartments of the host's macrophages, unless those m acrophages are appropriately activated. Despite the fact that protecti ve immunity can be induced by vaccination with crude parasite preparat ions, little progress has been made toward a defined vaccine for human s. In this study the gene encoding the Leishmania surface proteinase g p63 was cloned and expressed as a cytoplasmic protein in a bacille Cal mette-Guerin (BCG) vaccine strain. BALB/c and CBA/J mice were inoculat ed with a single dose of recombinant BCG and challenged with infective Leishmania major or Leishmania mexicana promastigotes. Significant pr otection was observed in both mouse strains against L. mexicana and in CBA/J against L. major, whereas only a delay in L. major growth was s een in BALB/c mice. Recombinant BCG also engendered a strong protectiv e response against challenge with amastigotes of L. mexicana, demonstr ating that the induced immune response recognized the intracellular fo rm of the parasite. The results support the view that recombinant BCG expressing gp63 may prove a useful vaccine for inducing protective cel l-mediated immune responses to Leishmania species causing American cut aneous leishmaniasis.