Development of adjuvant-combined nasal influenza vaccine

佐剂联合鼻流感疫苗的研制

• 批准号: 04557026
• 负责人: TAMURA Shinichi
• 金额: $ 12.61万
• 依托单位: National Institute of Health, Dept.of Pathology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557026/
• 关键词: influenza; intranasal vaccination; inactivated vaccine; adjuvant; heat-labile toxin; IgA; 交差感染阻止

Natural influenza virus has been shown to be superior to the inactivated vaccine for inducing cross-protection against variants within a subtype of A type virus. The cross-protection induced by natural infection seems to be largely due to the induction of cross-reacting IgA antibodies in the respiratory tract. These facts suggest that the development of immunization procedure to stimulate mucosal IgA antibody production would improve the protective efficacy of the current inactivated vaccine. In this regard, intranasal immunization of inactivated vaccine has been advocated as means of inducing secretory IgA and systemic IgG antibodies against influenza. However, the intranasal immunization of inactivated vaccine alone cannot easily generate the secretory IgA antibodies. Under these circumstances, we attempted to inoculate intranasally the current inactivated vaccine together with a potent adjuvant, cholera toxin B subunit (CTB) containing 0.1% of CT,in mice. The results demonstrated that the nasal administration of the adjuvant-combined vaccine into mice can mimic the efficacy of live virus in inducing cross-protection against variant virus challenge. Moreover, we examined the effect of the intranasal immunization of the adjuvant-combined vaccine on IgA and HI antibody responses in humans. The results demonstrated that the adjuvant-combined vaccine can elicit significantly not only secretory IgA antibody but also serum HI antibody, as compared with vaccine alone, in humans.

天然流感病毒已被证明在诱导对a型病毒亚型变异的交叉保护方面优于灭活疫苗。自然感染诱导的交叉保护似乎主要是由于呼吸道中IgA抗体的交叉反应。这些事实表明，发展免疫程序来刺激粘膜IgA抗体的产生将提高目前灭活疫苗的保护功效。在这方面，鼻内免疫灭活疫苗被提倡作为诱导分泌IgA和全身IgG抗体对抗流感的手段。然而，单独经鼻免疫灭活疫苗不能轻易产生分泌性IgA抗体。在这种情况下，我们尝试将目前的灭活疫苗与含有0.1% CT的强效佐剂霍乱毒素B亚单位（CTB）一起在小鼠中鼻内接种。结果表明，经鼻给药的佐剂联合疫苗可以模拟活病毒诱导对变异病毒攻击的交叉保护作用。此外，我们还研究了佐剂联合疫苗鼻内免疫对人IgA和HI抗体反应的影响。结果表明，与单独接种疫苗相比，佐剂联合疫苗不仅能显著诱导人分泌IgA抗体，还能显著诱导血清HI抗体。

项目成果

Asanuma,H.et al.: "Cross‐protection against influenza virus infection in mice vaccinated by combined nasal/subcutaneous administration." Vaccine. (in press). (1994)

Asanuma, H. 等人：“通过鼻/皮下联合疫苗对小鼠流感病毒感染进行交叉保护”（正在出版）。

Hirabayashi,Y.,et al.: "Involvement of antigen-presenting cells in the enhance-ment of the in vitro antibody responses by cholera toxin B subunit" Immunology. 75. 493-498 (1992)

Hirabayashi,Y.,et al.：“抗原呈递细胞参与霍乱毒素 B 亚基增强体外抗体反应”免疫学。

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)

Tamura, S.-I. 等人：“霍乱毒素 B 亚基和微量……增强流感疫苗免疫反应的机制”（出版中）。

Gizurarson,S.,et al.: "Stimulation of the transepithelial flux of influenza HA vaccine by cholera toxin B subunit" Vaccine. 10. 101-106 (1992)

Gizurarson,S.,et al.：“霍乱毒素 B 亚基对流感 HA 疫苗跨上皮通量的刺激”疫苗。

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。