Efficient protective immunity against Trypanosoma cruzi infection after nasal vaccination with recombinant Sendai virus vector expressing amastigote surface protein-2 |
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Authors: | Xuefeng Duan Yoshikazu Yonemitsu Bin Chou Kumi Yoshida Sakura Tanaka Mamoru Hasegawa Kohhei Tetsutani Hidekazu Ishida Kunisuke Himeno Hajime Hisaeda |
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Affiliation: | 1. Department of Parasitology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;2. Operating Unit for Clinical Trials of Gene Therapy, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;3. DNAVEC Corporation, Tsukuba, Ibaraki, Japan |
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Abstract: | Chagas’ disease, caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), is intractable showing a high mortality rate, and the development of effective vaccines is much desired. To examine the efficacy of a new mode of recombinant viral vaccine, we constructed two non-transmissible Sendai viruses (rSeV/dF) encoding the full-length parasite antigen amastigote surface protein-2 (ASP2) or ASP2 fused with a mono-ubiquitin on its N-terminus (UASP2). C57BL/6 mice immunized intranasally with rSeV/dF expressing either ASP2 or UASP2 showed significantly suppressed parasitemia and could be protected from lethal T. cruzi challenge. Depletion of CD8+ T cells around the time of infection with T. cruzi completely abolished this protection, confirming that acquired immunity against the infection of T. cruzi is dependent on CD8+ T cells. We also demonstrated that the protective immunity correlated with higher secretion of interferon-γ (IFN-γ) by spleen cells on in vitro-specific or non-specific stimulation. Increased CTL activity was also confirmed by degranulation or CTL assays. Interestingly, the control virus, rSeV/dF-GFP, induced even a higher IFN-γ production from spleen cells following non-specific but not specific stimulation in vitro, suggesting that SeV may also be a good adjuvant when used as a vaccine vehicle. Taking together, the current findings indicate that recombinant Sendai virus expressing the ASP2 or UASP2 antigens of T. cruzi are interesting candidates for the development of a new mode of recombinant viral vaccine against Chagas’ disease. |
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Keywords: | Trypanosoma cruzi Amastigote surface protein-2 Non-transmissible Sendai virus |
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