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

We have investigated the use of the protective antigen (PA) and lethal fact or (LF) components of anthrax toxin as a system for in,vivo delivery of cyt otoxic T-lymphocyte (CTL) epitopes. During intoxication, PA directs the tra nslocation of LF into the cytoplasm of mammalian cells. Here we demonstrate that antiviral immunity can be induced in BALB/c mice immunized with PA pl us a fusion protein containing the N-terminal 255 amino acids of LF (LFn) a nd an epitope from the nucleoprotein (NP) of lymphocytic choriomeningitis v irus. We also demonstrate that BALB/c mice immunized with a single LFn fusi on protein containing NP and listeriolysin O protein epitopes in tandem mou nt a CTL response against both pathogens. Furthermore,,ve show that NP-spec ific CTL are primed in both BALB/c and C57B/6 mice when the mice are immuni zed with a single fusion containing two epitopes, one presented by Ld and o ne presented by D-b. The data presented here demonstrate the versatility of the anthrax toxin delivery system and indicate that this system may be use d as a general approach to vaccinate outbred populations against a variety of pathogens.