Abstract

Attenuated Salmonella typhi are attractive for use as live vector vaccines to express protozoal antigens and deliver them to the human immune system. The gene encoding the mature form of Leishmania mexicana mexicana gp63 under control of tac promoter was integrated into the ΔaroC locus of the chromosome of attenuated ΔaroC, ΔaroD S. typhi strain CVD 908. After oral immunization of BALB c mice with two 1 × 10 9 colony forming unit doses given 21 days apart, CVD 908Ω( ΔaroC:: P tac -gp63) elicited a broad T cell-mediated immune response against L. m. mexicana gp63 as demonstrated by: (1) lymphoproliferative response to fixed whole L. m. mexicana promastigotes; (2) activation of IL-2 (but not IL-4)-producing lymphocytes; (3) appearance of cytotoxic T cells against mouse mastocytoma cells expressing gp63. This T-cell mediated immune response was associated with significant protection in F1(BALB/cXC57Bl/6) mice challenged in their footpads with a wild type strain of L. m. mexicana.

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