Studies on the development of mucosal vaccine adjuvant

• Project/Area Number: 06670339
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: National Institute of Health
• Principal Investigator: TAMURA Shinichi National Institute of Health Dept.of Pathol., Head, 感染病理部, 室長 (20100084)
• Co-Investigator(Kenkyū-buntansha): KURATA Takeshi National Institute of Health Dept.of Pathol., Director, 感染病理部, 室長 (50012779)
• Project Period (FY): 1994 – 1995
• Project Status: Completed (Fiscal Year 1995)
• Budget Amount: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: Cholera toxin / heat-labile toxin / adjuvant / influenza / nasal vacccine / IgA / 変異LT / コレラトキシンBサブユニット

Research Abstract

Cholera toxin B subunit (CTB) or Escherichia coli heat-labile toxin (LTB) (2mug) , each supplemented with a trace amount of the holotoxin (0.02-20ng) , were examined for the adjuvant effect on antibody responses against influenza inactivated vaccine in BALB/c mice.Each mouse received a primary intranasal (i.n.) inoculation with the vaccine (1.5mug) , prepared from PR8 (H1N1) virus, together with the toxin-containing B subunit and in 4 weeks a second i.n.inoculation of the vaccine alone.The inoculation of the vaccine with the toxin-containing the B subunit induced significantly high primary and secondary anti-HA lgA and lgG Ab responses in the nasal wash and serum, while the vaccine with the B subunit or less than 2 ng of the toxin induced little response.The synergistic adjuvant effect was maximal in the concentration of the B subunit supplemented with 0.2-2 ng of the toxin.Under these conditions, the augmented lgA and lgG Ab responses, which are cross-protective to PR8 HA molecules provided complete cross-protection against PR8 virus challenge in mice immunized with heterologous vaccines within the same subtype.These results suggest that CTB or LTB containing a trace amount of CT or LT can be used as a potent adjuvant for nasal vaccination of human against influenza.

Research Products

• [Publications] Tamura, S. -I. et al.: "Synergistic action of cholera toxin B subunit (and E. coli heat-labile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine" Vaccine. 12. 419-426 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamura, S. -I. et al.: "Escherichia coliheat-labile enterotoxin B subunits supplemented with a tra ; ce amount of the holotoxin as an adjuvant for nasal influenza vaccine" Vaccine. 12. 1083-1089 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamura, S. -I. et al.: "Effect of cholera toxin adjuvant on IgE antibody response to orally or nasally administered ovalbumin" Vaccine. 13. 1238-1240 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamura, S. -I. et al.: "The mechanism of enhancement of the immune responses to influenza vaccine with cholera toxin B subunit and a trace amount of holotoxin" Vaccine. 13. 339-341 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Asanuma, H. et al.: "Characterization of mouse nasal lymphocytes isolated byenzymatic extraction with collagenase" J. Immunol. Methods. 187. 41-51 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hashiguchi, K. et al.: "Antibodyresponses in volumteers induced by nasal influenza vaccine combined with Escherichia coliheat-labile enterotoxin B subunit containing a trace amount of the holotoxin" Vaccine. (in press). (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamura, S.-I. et al.: "Synergistic action of cholera toxin B subunit (and E. coli heat-labile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine" Vaccine. 12. 419-426 (1994)
• [Publications] Tamura, S.-I. et al.: "Escherichia coli heat-labile enterotoxin B subunits supplemented with a tra ; ce amount of the holotoxin as an adjuvant for nasal influenza vaccine" Vaccine. 12. 1083-1089 (1994)
• [Publications] Tamura, S.-I. et al.: "Effect of cholera toxin adjuvant on IgE antibody response to orally or nasally administered ovalbumin" Vaccine. 13. 1238-1240 (1994)
• [Publications] Tamura, S.-I. et al.: "The mechanism of enhancement of the immune responses to influenza vaccine with cholera toxin B subunit and a trace amount of holotoxin" Vaccine. 13. 339-341 (1995)
• [Publications] Asanuma, H. et al.: "Characterization of mouse nasal lymphocytes isolated byenzymatic extraction with collagenase" J. Immunol. Methods. 187. 41-51 (1995)
• [Publications] Hashiguchi, K. et al.: "Antibodyresponses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin" Vaccine. (in press). (1995)
• [Publications] Tamura,S.-I.et al.: "Formulation of inactivated influenza vaccines for providing effective cross-protection by intranasal vaccination in mice." Vaccine. 12. 310-316 (1994)
• [Publications] Tamura,S.-I.et al.: "Synergistic action of cholera toxin B subunit (and E.coli heat-labile toxin B subunit) and a trace amount of cholera." Vaccine. 12. 419-426 (1994)
• [Publications] Tamura,S.-I.et al.: "E.coli heat-labile enterotoxin B subunits supplemented with a trace amount of the holotoxin as an adjuvant for nasal influ…" Vaccine. 12. 1083-1089 (1994)
• [Publications] Tamura,S.-I.et al.: "Effect of cholera toxin adjuvant on IgE antibody response to orally or nasally administered ovalbumin." Vaccine. 12. 1234-1240 (1994)
• [Publications] Tamura,S.-I.et al.: "Mechanism of enhancement of the immune responses to influenza vaccine with cholera toxin B subunit and a trace amount of ……" Vaccine. (in press). (1994)
• [Publications] Asanuma,H.et al.: "Cross-protection against influenza virus infection in mice vaccinated by combined nasa1/subcutaneous administration." Vaccine. (in press). (1994)