Quantitative and qualitative features of heterologous virus-vector-induced antigen-specific CD8+ T cells against Trypanosoma cruzi infection.
We studied some aspects of the quantitative and qualitative features of heterologous recombinant (re) virus-vector-induced, antigen-specific CD8(+) T cells against Trypanosoma cruzi. We used three different, highly attenuated re-viruses, i.e., influenza virus, adenovirus and vaccinia virus, which all expressed a single, T. cruzi antigen-derived CD8(+) T-cell epitope. The use of two out of three vectors or the triple virus-vector vaccination regimen not only confirmed that the re-vaccinia virus, which was placed last in order for sequential immunisation, was an effective booster for the CD8(+) T-cell immunity in terms of the number of antigen-specific CD8(+) T cells, but also demonstrated that (i) the majority of cells exhibit the effector memory (T(EM)) phenotype, (ii) robustly secrete IFN-γ, (iii) express higher intensity of the CD122 molecule and (iv) present protective activity against T. cruzi infection. In contrast, placing the re-influenza virus last in sequential immunisation had a detrimental effect on the quantitative and qualitative features of CD8(+) T cells. The triple virus-vector vaccination was more effective at inducing a stronger CD8(+) T-cell immunity than using two re-viruses. The different quantitative and qualitative features of CD8(+) T cells induced by different immunisation regimens support the notion that the refinement of the best choice of multiple virus-vector combinations is indispensable for the induction of a maximum number of CD8(+) T cells of high quality.
Takayama
Eiji
E
Department of Global Infectious Diseases and Tropical Medicine, National Defense Medical College, Tokorozawa City, Saitama, Japan.
Ono
Takeshi
T
Carnero
Elena
E
Umemoto
Saori
S
Yamaguchi
Yoko
Y
Kanayama
Atsuhiro
A
Oguma
Takemi
T
Takashima
Yasuhiro
Y
Tadakuma
Takushi
T
García-Sastre
Adolfo
A
Miyahira
Yasushi
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology* / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D051379:Mice; D009975:Orthomyxoviridae / Q000235:genetics; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014616:Vaccinia virus / Q000235:genetics; D014780:Viruses / Q000235:genetics*
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D053646:Interleukin-2 Receptor beta Subunit; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D007371:Interferon-gamma