Effective immunization against cutaneous leishmaniasis with recombinant bacille Calmette-Guerin expressing the Leishmania surface proteinase gp63

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 24; pp. 11473 - 11477
• Main Authors: Connell, N.D, Medina-Acosta, E, McMaster, W.R, Bloom, B.R, Russell, D.G
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.12.1993; National Acad Sciences; National Academy of Sciences
• Subjects: ADN RECOMBINADO; ADN RECOMBINE; Amastigotes; Animals; BCG Vaccine - administration & dosage; Biological and medical sciences; Cloning, Molecular; Cutaneous leishmaniasis; Disease; EXPRESION GENICA; EXPRESSION DES GENES; Heat-Shock Proteins - genetics; Human protozoal diseases; Humans; IMMUNITE CELLULAIRE; Immunity (Disease); INFECCIONES POR PROTOZOOS; Infections; Infectious diseases; INMUNIDAD CELULAR; Inoculation; LEISHMANIA; Leishmania major - genetics; Leishmania major - immunology; LEISHMANIA MEXICANA; Leishmania mexicana - genetics; Leishmania mexicana - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - prevention & control; Leshmaniasis; Lesions; Medical research; Medical sciences; Metalloendopeptidases - administration & dosage; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Microscopy, Immunoelectron; Mycobacterium bovis - genetics; Mycobacterium bovis - ultrastructure; Parasites; Parasitic diseases; Promastigotes; PROTEASAS; PROTEASE; Protozoal diseases; Protozoan Proteins - administration & dosage; PROTOZOOSE; RATON; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - immunology; SOURIS; T lymphocytes; Time Factors; VACCIN VIVANT; VACCINATION; Vaccines; Vaccines, Synthetic - administration & dosage; VACUNA VIVA; VACUNACION; Immunoprotection; Recombinant microorganism; Protozoa; Protozoal disease; Immunization; Enzyme; Rodentia; BCG; Vaccine; Leishmaniasis; Cell surface; Leishmania mexicana; Infection; Vertebrata; Mammalia; Mouse; Rhizoflagellata; Hydrolases; Proteinases; Leishmania major
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.24.11473

Leishmania parasites cause a spectrum of diseases that afflict the populations of 86 countries in the world. The parasites can survive within the lysosomal compartments of the host's macrophages, unless those macrophages are appropriately activated. Despite the fact that protective immunity can be induced by vaccination with crude parasite preparations, little progress has been made toward a defined vaccine for humans. In this study the gene encoding the Leishmania surface proteinase gp63 was cloned and expressed as a cytoplasmic protein in a bacille Calmette-Guerin (BCG) vaccine strain. BALB/c and CBA/j mice were inoculated with a single dose of recombinant BCG and challenged with infective Leishmania major or Leishmania mexicana promastigotes. Significant protection 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 seen in BALB/C mice. Recombinant BCG also engendered a strong protective response against challenge with amastigotes of L. mexicana, demonstrating that the induced immune response recognized the intracellular form of the parasite. The results support the view that recombinant BCG expressing gp63 may prove a useful vaccine for inducing protective cell-mediated immune responses to Leishmania species causing American cutaneous leishmaniasis