| Project/Area Number |
10670266
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Nagoya City University |
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Principal Investigator |
TOCHIKUBO Kunio Nagoya City University Medical School, Department of Microbiology, Professor, 医学部, 教授 (30079991)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Yutaka Nagoya City University Medical School, Department of Molecular Neurobiology, Junior Assistant Professor, 医学部, 助手 (90285198)
KOZUKA Satoshi Chukyo Women's University, Faculty of Wellness, Department of Nutrition, Associate Professor, 健康科学部, 助教授 (40117817)
YASUDA Yoko Nagoya City University Medical School, Department of Microbiology, Associate Professor, 医学部, 助教授 (70080009)
GOTO Norihisa National Institute of Infectious Diseases, Department of Safety Research on Biologics, Chief, 安全性研究部, 室長 (10100108)
TANIGUCHI Tooru Nagoya City University Medical School, Department of Microbiology, Junior Assistant Professor, 医学部, 助手 (00285199)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Recombinant CTB / Mucosal adjuvant / Intranasal administration / Mucosal vaccine / Tetanus toxoid / Diphtheria toxoid / Hepatitis B vaccine / CFA / III |
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| Research Abstract |
For the purpose of changing the immunization procedure of several vaccines from subcutaneous injection, which have been in practice for a long time, to intranasal administration, we have been examining systemic and mucosal immune responses of mice to some vaccines inoculated intranasally with recombinant cholera toxin B subunit (rCTB). Intranasal co-administration of rCTB with tetanus toxoid (TT), diphtheria toxoid (DT), pertussis component vaccine or hepatitis B vaccine (HBV) induced high levels of vaccine-specific serum IgG and mucosal IgA antibody titers. Moreover, a combination of rCTB with TT and DT provided complete protection against tetanus toxin challenge and diphtheria antitoxin titers above a protective level of 0.1 IU/ml, respectively. Intranasal immunization of HBV with rCTB also provided serum anti-HBV antibody titers above 100 mIU/ml protective in people at increased risk or displaying risk behavior. Pilus colonization factor antigen (CFA/III) of human enterotoxigenic Es
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cherichia coli (ETEC) was incorporated into the nasal mucosal epithelium without rCTB and induced CFA/ III-specific serum IgG and mucosal IgA antibody, suggesting the possibility of intranasal vaccine for preventing the disease produced by the ETEC.When five intranasal immunizations of rCTB and TT and subsequent five intranasal administrations with rCTB plus DT were performed, anti-rCTB antibodies induced by the previous vaccination did not have any effects upon the production of anti-DT antibodies, especially, at long intervals between two kinds of inoculations. Recombinant CTB elicited no toxic effects to macrophages and no vascular permeability-increasing effects. Moreover, no distinct local histopathological reactions were observed in the nasal cavity, the small-intestinal loop or the muscle given rCTB.These facts indicate that rCTB is a safe and useful candidate as a mucosal vaccine adjuvant.
We finished constructing an efficient synthesis and secretion system for Shiga toxin I and II B subunits of enterohemorrhagic E.coli (EHEC) usins Bacillus brevis and have been purifing them to develop intranasal or oral vaccine for preventing hemorrhagic colitis and hemolytic-uremic syndrome produced by EHEC. Less
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