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, we show that NP-specific CTL are primed in both BALB/c and C57BL/6 mice when the mice are immunized with a single fusion containing two epitopes, one presented by Ld and one presented by Db. 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.
Doling
A M
AM
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ballard
J D
JD
Shen
H
H
Krishna
K M
KM
Ahmed
R
R
Collier
R J
RJ
Starnbach
M N
MN
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001427:Bacterial Toxins; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin