IMMUNOGENICITY OF A SALMONELLA-TYPHI CVD-908 CANDIDATE VACCINE STRAINEXPRESSING THE MAJOR SURFACE PROTEIN GP63 OF LEISHMANIA-MEXICANA MEXICANA

Attenuated Salmonella typhi are attractive for use as live vector vacc ines to express protozoal antigens and deliver them to die human immun e system. The gene encoding the mature form Of Leishmania mexicana mex icana gp63 under control of tac promoter was integrated into the Delta aroC locus of the chromosome of attenuated Delta aroC, Delta aroD S. typhi strain CVD 908. After or al immunization of BALB/c mice with two 1x10(9) colony forming unit doses given 21 days apart, CVD 908 Omega( Delta aroC::P-tac-gp63) elicited a broad T cell-mediated immune respon se against L, m, mexicana gp63 as demonstrated by: (1) lymphoprolifera tive response to fixed whole L, m, mexicana promastigotes; (2) activat ion of IL-2 (but not IL-4)-producing lymphocytes; (3) appearance of cy totoxic T cells against mouse mastocytoma cells expressing gp63, This T-cell mediated immune response was associated with significant protec tion in F1(BALB/cXC57B1/6) mice challenged in their footpads with a wi ld type sti-ain of L, m, mexicana (C) 1998 Elsevier-Science Ltd. All r ights reserved.