Actively induced antigen-specific CD8+ T cells by epitope-bearing parasite pre-infection but not prime/boost virus vector vaccination could ameliorate the course of Plasmodium yoelii blood-stage infection
| Autor: | Yasuhiro Takashima, Takeshi Ono, Yasushi Miyahira, Yoko Yamaguchi, Takemi Oguma, Eiji Takayama, Takushi Tadakuma |
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| Rok vydání: | 2012 |
| Předmět: |
Male
T cell Genetic Vectors Epitopes T-Lymphocyte Vaccinia virus CD8-Positive T-Lymphocytes Parasitemia Major histocompatibility complex Epitope Adenoviridae Viral vector Mice Interleukin 21 Malaria Vaccines parasitic diseases medicine Animals Cytotoxic T cell Drug Carriers Mice Inbred BALB C Vaccines Synthetic General Veterinary General Immunology and Microbiology biology Public Health Environmental and Occupational Health Viral Vaccines Plasmodium yoelii biology.organism_classification Virology Malaria Infectious Diseases medicine.anatomical_structure Immunology biology.protein Molecular Medicine CD8 |
| Zdroj: | Vaccine. 30:6270-6278 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2012.08.009 |
| Popis: | The lack of MHC molecules on red blood cells (RBCs) has led to questions regarding the immunological function of CD8(+) T cells against malarial blood-stage (MBS). However, several recent reports contradicting with this concept have suggested that they play an important role in the course of MBS infection. The present study generated genetically engineered murine malaria, Plasmodium yoelii, which expresses a well-defined Trypanosoma cruzi-derived, H-2K(b)-restricted CD8(+) T cell epitope, ANYNFTLV. Prime/boost vaccination by the use of recombinant adenovirus and recombinant modified vaccinia virus Ankara (MVA), which induced an enhanced number of ANYNFTLV-specific CD8(+) T cells, failed to prevent a pathological outcome to occur upon ANYNFTLV-expressing murine MBS infection. This outcome did not change even with the combination of passive transfer of an appreciable number of in vitro-expanded ANYNFTLV-specific CD8(+) T cells. In contrast, the pre-infection of mice with T. cruzi, which intrinsically bears the same CD8(+) T cell epitope significantly improved the survival of ANYNFTLV-expressing malaria-infected mice but not that of control malaria-infected ones. This protective effect was abrogated by the use of a CD8(+) T cell-depleting monoclonal antibody. Although the protective effect was observed only in certain situations, the actively induced antigen-specific CD8(+) T cells could ameliorate the pathologies caused by the MBS. This is the first study to implicate that the active induction of antigen-specific CD8(+) T cells should be included in the development of a vaccine against MBS. |
| Databáze: | OpenAIRE |
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