| Co-Investigator(Kenkyū-buntansha) |
GOTO Norihisa National Institute of Infectious Diseases, Department of Safety Research on Blood and Biological Products, Chief, 血液・安全性研究部, 室長 (10100108)
TANIGUCHI Tooru Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究科, 助手 (00285199)
TOCHIKUBO Kunio Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (30079991)
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| Research Abstract |
We have developed a safe and stable mucosal adjuvant, recombinant cholera toxin B subunit (rCTB) and shown its effectivity on induction of protective immunity in mice by nasal co-administration of tetanus toxoid, diphtheria toxoid, acellular pertussis vaccine, hepatitis B surface antigen and influenza vaccine. In this study, we examined pili, inactivated whole-cells and toxin subunit as vaccine canditates and rCTB as an adjuvant for developing mucosal vaccines against diarrheagenic Escherichia coli infections.
1. Enterotoxigenic Escherichia coli (ETEC) (1) Mice immunized nasally with purified pili, colonization factor antigen III (CFA/III) pili ± rCTB raised serum anti-pili IgG and IgA. These antibodies agglutinated ETEC cells, indicating that opsonization and inhibition of colonization may be possible. (2) Nucleotide sequence of whole region for CFA/III formation was determined and function of the 14 genes of the operon was analysed. A cofJ mutant formed pili, but did not adhere to Caco-2 cells, showing that cofJ encodes adhesin of the pili. (3) Recombinant CofJ adhered to the cells and anti-CofJ IgG(Fab) could inhibit the adhesion. (4) Nasal vaccination of CofJ + rCTB is in progress.
2. Enterohemorrhagic E. Coli(EHEC) O157 (1) Mice received formalin-inactivated EHEC whole-cells ± rCTB nasally and orally, raised serum IgG antibody. Nasal route was more effective than oral one, showing applicability to other pathogens of nasal whole-cell vaccines. (2) Recombinant Shiga toxin B subunits (rStx1B, rStx2B) were produced. (3) Mice immunized nasally with rStx1B ± rCTB raised serum antibody, indicating possible prevention of hemolytic uremic syndrome and encephalopathy by neutralization of Shiga toxin. (3)rStx1B showed mucosal adjuvanticity. (5) As induction of mucosal IgA against whole-cells and Stx1B was hardly observed, composition of vaccine candidates should be improved.
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