Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection.
In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFkappaB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection.
Miyahira
Yasushi
Y
Atopy Research Center, Department of Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. miyahira@med.juntendo.ac.jp
Takashima
Yasuhiro
Y
Kobayashi
Seiki
S
Matsumoto
Yasunobu
Y
Takeuchi
Tsutomu
T
Ohyanagi-Hara
Mutsuko
M
Yoshida
Ayako
A
Ohwada
Akihiko
A
Akiba
Hisaya
H
Yagita
Hideo
H
Okumura
Ko
K
Ogawa
Hideoki
H
D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology* / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007117:Immunization, Secondary; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014349:Trypanosoma cruzi / Q000276:immunology*; D014611:Vaccination; D019562:Viral Load
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse