Efficient protective immunity against Trypanosoma cruzi infection after nasal vaccination with recombinant Sendai virus vector expressing amastigote surface protein-2.
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-gamma (IFN-gamma) 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-gamma 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.
Duan
Xuefeng
X
Department of Parasitology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yonemitsu
Yoshikazu
Y
Chou
Bin
B
Yoshida
Kumi
K
Tanaka
Sakura
S
Hasegawa
Mamoru
M
Tetsutani
Kohhei
K
Ishida
Hidekazu
H
Himeno
Kunisuke
K
Hisaeda
Hajime
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000276:immunology*; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; C493236:ASP-2 protein, Trypanosoma cruzi; D009439:Neuraminidase