2012 Fiscal Year Final Research Report
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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| Keywords | 感染防御 / ワクチン / 動物モデル |
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| 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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Research Products
(4 results)
