Quantitative and qualitative features of heterologous virus-vector-induced antigen-specific CD8+ T cells against Trypanosoma cruzi infection

Int J Parasitol. 2010 Nov;40(13):1549-61. doi: 10.1016/j.ijpara.2010.05.011. Epub 2010 Jul 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Chagas Disease / immunology*
  • Chagas Disease / prevention & control*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Genetic Vectors*
  • Immunization, Secondary / methods
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Interleukin-2 Receptor beta Subunit / metabolism
  • Mice
  • Orthomyxoviridae / genetics
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Trypanosoma cruzi / immunology*
  • Vaccination / methods
  • Vaccinia virus / genetics
  • Viruses / genetics*

Substances

  • Antigens, Protozoan
  • Epitopes, T-Lymphocyte
  • Interleukin-2 Receptor beta Subunit
  • Protozoan Vaccines
  • Recombinant Proteins
  • Interferon-gamma