Studies on the development of mucosal vaccine adjuvant

粘膜疫苗佐剂的研制研究

• 批准号: 06670339
• 负责人: TAMURA Shinichi
• 金额: $ 1.41万
• 依托单位: National Institute of Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670339/
• 关键词: 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

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.

在BALB/c小鼠中检测霍乱毒素B亚单位（CT B）或大肠杆菌不耐热毒素（LTB）（2 μ g）（各自补充有痕量的全毒素（0.02- 20 ng））对针对流感灭活疫苗的抗体应答的佐剂作用。接种疫苗（1.5 μ g），其由PR 8（H1N1）病毒制备，与含毒素的B亚单位一起，并在4周内第二次单独i.n.接种疫苗。接种含毒素的B亚单位的疫苗在鼻洗液和血清中诱导显著高的初次和二次抗HA IgA和IgG Ab应答，而含B亚单位或少于2ng毒素的疫苗几乎不诱导免疫应答，在B亚单位浓度下添加0.2- 2ng毒素的协同佐剂效应最大，在此条件下，增强的IgA和IgG抗体应答，结果表明，含有微量CT或LT的CTB或LTB可作为人流感疫苗的有效佐剂。

项目成果

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)

田村，S.-I。

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)

田村，S.-I。

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)

Hashiguchi, K. 等人：“鼻流感疫苗与含有微量全毒素的大肠杆菌不耐热肠毒素 B 亚基联合诱导的志愿者抗体反应”疫苗。

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)

田村，S.-I。

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)

田村，S.-I。