RECOMBINANT BCG EXPRESSING THE LEISHMANIA SURFACE-ANTIGEN GP63 INDUCES PROTECTIVE IMMUNITY AGAINST LEISHMANIA-MAJOR INFECTION IN BALB C MICE/

We have cloned and expressed the gp63 gene of Leishmania major in BCG to develop a recombinant vaccine against zoonotic cutaneous leishmania sis. Two different expression systems were investigated. The first sys tem consists of pAN, a Mycobacterium paratuberculosis promoter, which drives expression of ORF2, an open reading frame in IS900. This system allows the production of heterologous polypeptides as hybrids with th e ORF2 gene product. The second expression system relies on the produc tion of antigenic fragments as fusion proteins with the N-terminal reg ion of Mycobacterium fortuitum beta-lactamase. Both constructs resulte d in the production of Gp63 in BCG. The ability of the two recombinant BCG strains to induce protective immunity against a challenge with L. major amastigotes was evaluated after vaccination of susceptible (BAL B/c), and resistant (C57BL/6) mice. Recombinant BCC producing Gp63 as a hybrid protein with the N-terminal region of the beta-lactamase elic ited significant protection against a challenge with L. major in BALB/ c-immunized mice.