Studies on the Development of Spray Influenza Vaccine Combined with an Adjuvant

佐剂喷雾型流感疫苗的研制

• 批准号: 01570260
• 负责人: TAMURA Shin-ichi
• 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: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570260/
• 关键词: Cholera toxin B subunit; HA vaccine; Nasal vaccination; Haemagglutinin; IgA抗体; インフルエンザHAワクチン

Effects of intransal inoculation of influenza HA vaccine, together with cholera toxin B subunit (CTB), on antibody responses to virus antigens and on protection against viral challenge were investigated in Balb/c mice.(1) The vaccine inoculated with CTB induced high responses of both antiviral IgA antibodies in the nasal wash and haemagglutinin-inhibiting (HI) antibody in the serum, enough to provide complete protection against viral challenge 4 weeks after immunization. (2) High levels of antibody were maintained for more than 16 weeks after inoculation, affording complete protection during this interval. (3) The inoculation of HA vaccine prepared from a variant virus within the same subtype or a different subtype virus, together with CTB, provided partial protection against viral infection, with production of antiviral cross-reacting IgA antibodies. (4) The two-dose regimen, composed of a primary internasal inoculation of vaccine together with CTB and the subsequent inoculation of va … More ccine alone 4 weeks later, induced much higher responses of both antiviral IgA antibodies in nasal wash and HI antibody in serum, which persisted for more than 12 weeks after the second inoculation. This regimen provided not only complete protection against homologous virus infection, but also partial cross-protection against heterologous A-type virus infection, in parallel with high persistent levels of cross-reacting IgA antibodies.Intranasal inoculation of haemagglutinin (HA) molecules, purified from virus, together with CTB into mice resulted in complete protection against viral infection in parallel with the induction of high levels of HA-specific IgA-specific IgA and IgG antibodies on the respiratory tract. The respiratory tract IgA, purified from nasal and lung washings, included cross-reacting antibodies besides specific antibodies, which were not only higher in content in the nasal wash, but also more cross-reactive than IgG. When passively transferred to normal mouse before infection, the purified IgA protected against viral challenge.These results suggest that intranasal vaccination of CTB-combined influenza inactivated vaccine or HA molecules, which consists of different subtype viruses and different type viruses, is very useful for controlling the outbreaks of influenza by inducing locsl IgA antibodies. Less

在BalB/c小鼠中研究了流感HA疫苗和霍乱毒素B亚单位（CT B）的体内接种对病毒抗原的抗体应答和对病毒攻击的保护作用。(1)用CTB接种的疫苗诱导鼻洗液中的抗病毒伊加抗体和血清中的血凝素抑制（HI）抗体的高应答，足以在免疫后4周提供针对病毒攻击的完全保护。(2)高水平的抗体在接种后维持超过16周，在此期间提供完全保护。(3)从相同亚型或不同亚型病毒中的变异病毒制备的HA疫苗与CTB一起接种，提供了针对病毒感染的部分保护，并产生抗病毒交叉反应伊加抗体。(4)两剂方案包括疫苗和CTB的初次鼻内接种和随后的疫苗接种。 ...更多信息 单独接种后4周，鼻洗液中的抗病毒伊加抗体和血清中的HI抗体均诱导了更高的应答，这种应答在第二次接种后持续超过12周。该方案不仅提供了针对同源病毒感染的完全保护，而且还提供了针对异源A型病毒感染的部分交叉保护，同时具有高持续水平的交叉反应伊加抗体。与CTB一起注射到小鼠体内，导致对病毒感染的完全保护，同时诱导高水平的HA特异性伊加-呼吸道上的特异性伊加和IgG抗体。从鼻洗液和肺洗液中纯化的呼吸道伊加除含有特异性抗体外，还含有交叉反应性抗体，不仅含量较高，而且交叉反应性也较IgG强。这些结果表明，鼻内接种由不同亚型病毒和不同类型病毒组成的CTB-流感灭活疫苗或HA分子，可通过诱导局部伊加抗体来控制流感的爆发。少

项目成果

Tamura, S.ーI.,et al.: "Enhancement of protective antibody responses by cholera toxin B subunit inoculated intranasally with influenza vaccine" Vaccine. 7. 257-262 (1989)

Tamura, S.-I. 等人：“通过鼻内接种流感疫苗来增强保护性抗体反应”疫苗。7. 257-262 (1989)

Tamura, S. -I. et al: "Enhancement of protective antibody responses by cholera toxin B subunit inoculated intranasally with influenza vaccine" Vaccine. 7. 257-262 (1989)

田村，S.-I。

Tamura, S. -I. et al: "Functional role of respiratory tract haemagglutininspecific IgA antibodies in protection against influenza" Vaccine. 8. 479-485 (1990)

田村，S.-I。

Tamura, S.ーI., et al.: "Protection against influenza virus infection by a twoーdose regimen of nasal vaccination using vaccines combined with cholera toxin B subunit" Vaccine. 7. 314-320 (1989)

Tamura, S.-I. 等人：“通过使用与霍乱毒素 B 亚单位组合的疫苗进行两剂鼻疫苗接种方案来预防流感病毒感染”疫苗。

Tamura, S. -I. et al: "Effectiveness of cholera toxin B subunit as an adjuvant for nasal influenza vaccination despite pre-existing immunity to CTB" Vaccine. 7. 503-506 (1989)

田村，S.-I。