Cytotoxic T-lymphocyte epitopes fused to anthrax toxin induce protective antiviral immunity

We have investigated the use of the protective antigen (PA) and lethal factor (LF) components of anthrax toxin as a system for in,vivo delivery of cytotoxic T-lymphocyte (CTL) epitopes. During intoxication, PA directs the translocation of LF into the cytoplasm of mammalian cells. Here we demonstrate that antiviral immunity can be induced in BALB/c mice immunized with PA plus a fusion protein containing the N-terminal 255 amino acids of LF (LFn) and an epitope from the nucleoprotein (NP) of lymphocytic choriomeningitis virus. We also demonstrate that BALB/c mice immunized with a single LFn fusion protein containing NP and listeriolysin O protein epitopes in tandem mount a CTL response against both pathogens. Furthermore,,ve show that NP-specific CTL are primed in both BALB/c and C57B/6 mice when the mice are immunized with a single fusion containing two epitopes, one presented by Ld and one presented by D-b. The data presented here demonstrate the versatility of the anthrax toxin delivery system and indicate that this system may be used as a general approach to vaccinate outbred populations against a variety of pathogens.