Study for side effects of inactivated SARS-CoV vaccine.
| Project/Area Number |
22790444
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
IWATA Naoko 国立感染症研究所, 感染病理部, 主任研究官 (10360695)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,456,279 (Direct Cost: ¥3,427,907、Indirect Cost: ¥1,028,372)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥556,279 (Direct Cost: ¥427,907、Indirect Cost: ¥128,372)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 感染防御 / ワクチン / 動物モデル / ウイルス / 感染症 |
|---|
| Research Abstract |
Severe acute respiratory syndrome-related coronavirus (SARS-CoV) is an emerging pathogen that causes severe respiratory illness. Whole UV-inactivated SARS-CoV (UV-V), bearing multiple epitopes and proteins, is a candidate vaccine against this virus. However, whole inactivated SARS vaccine that includes nucleocapsid protein is reported to induce eosinophilic infiltration in mouse lungs after challenge with live SARS-CoV. In this study, an ability of Toll-like receptor (TLR) agonists to reduce the side effects of UV-V vaccination in a 6-month-old adult BALB/c mouse model was investigated, using the mouse-passaged Frankfurt 1 isolate of SARS-CoV. Immunization of adult mice with UV-V, with or without alum, resulted in partial protection from lethal doses of SARS-CoV challenge, but extensive eosinophil infiltration in the lungs was observed. By contrast, TLR agonists added to UV-V vaccine, including lipopolysaccharide, polyU, and poly (I:C) (UV-V+TLR), strikingly reduced excess eosinophilic infiltration in the lungs and induced lower levels of interleukin-4 and -13 and eotaxin in the lungs than UV-V-immunization alone.Additionally, microarray analysis showed that genes associated with chemotaxis, eosinophil migration, eosinophilia, and cell movement, and the polarization of Th2 cells were up-regulated in UV-V- but not in UV-V+TLR-immunized mice. Rather, genes downstream of TLR3 and TLR4 were up-regulated in UV-V+TLR- compared with UV-V-immunized mice. These findings suggest that vaccine-induced eosinophil immunopathology in the lungs upon SARS-CoV infection can be avoided by the TLR agonists adjuvant.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Association of major histocompatibility complex class I haplotypes with disease progression after simian immunodeficiency virus challenge in Burmese rhesus macaques2012
Author(s)
Nomura, T., Yamamoto, H., Shiino, T., Takahashi, N., Nakane, T., Iwamoto, N., Ishii, H., Tsukamoto, T., Kawada, M., Matsuoka, S., Takeda, A., Terahara, K., Tsunetsugu-Yokota, Y., Iwata-Yoshikawa, N., Hasegawa, H., Sata, T., Naruse T.K., Kimura, A., Matano, T.
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Journal Title
Journal of Virology
Volume: (in press)
Issue: 12
Pages: 6481-90
DOI
Related Report
Peer Reviewed
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[Presentation] Immune response against EEV and IMV in non-human primates vaccinated with a highly attenuated smallpox vaccine LC16m8 and protection from lethal monkeypox2011
Author(s)
Masayuki Saijo, Yasushi Ami, Yuriko Suzaki, Noriyo Nagata, Naoko Yoshikawa (Iwata), Hideki Hasegawa, Momoko Ogata, Shuetsu-Fukushi, Tetsuya Mizutani, Tetsutaro Sata, Ichiro Kurane, Shigeru Morikawa
Organizer
International Union of Microbiological Societies 2011 Congress
Place of Presentation
Sapporo
Related Report
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