Development of influenza live vaccine by reverse genetics

通过反向遗传学开发流感活疫苗

• 批准号: 13557023
• 负责人: KAWAOKA Yoshihiro
• 金额: $ 9.02万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557023/
• 关键词: influenza virus; reverse genetics; live vaccine; A型インフルエンザウイルス; M2膜蛋白質; M2蛋白質; 膜貫通領域

Influenza virus is a highly infectious respiratory pathogen of birds and mammals, including human. It often produces significant mobidity and mortality in humans. Current methods of immunization against influenza virus include parental administration of inactivated influenza virus vaccines, which reduces the incidence of clinical illness in healthy subjects. But in some cases, immunization with inactivated vaccines is associated with very low protection rates or short protection periods.Another promising approach to vaccination is the use of live-attenuated influenza viruses. Theses vaccines have shown considerable promise in ongoing clinical trials. However, it has been concerned that the pathogenesis happened to recovered during their replication.We propose an alternative approach to the design of live virus vaccines, one that relies on alteration of the influenza A virus M2 protein which is responsible for ion channel activity. It did not show appreciable growth defect in cell culture, although its growth was attenuated in mice. It has shown that this M2 ion channel defective mutant virus protected mice against challenge with lethal doses of influenza virus, indicating the potential or incorporating this M2 alteration in a live influenza vaccine as one of the attenuating mutations.

流感病毒是鸟类和哺乳动物包括人类的高度传染性呼吸道病原体。它经常在人类中产生显著的发病率和死亡率。目前针对流感病毒的免疫接种方法包括父母给予灭活流感病毒疫苗，这降低了健康受试者中临床疾病的发生率。但在某些情况下，灭活疫苗的免疫保护率很低或保护期很短。另一种有希望的疫苗接种方法是使用减毒活流感病毒。这些疫苗在正在进行的临床试验中显示出相当大的前景。然而，人们一直担心的是，发病机制发生恢复在他们的replication.We提出了一种替代的方法来设计活病毒疫苗，一个依赖于改变的流感病毒M2蛋白，这是负责离子通道活性。它在细胞培养中没有表现出明显的生长缺陷，尽管它在小鼠中的生长减弱。已经显示，这种M2离子通道缺陷型突变病毒保护小鼠免受致死剂量流感病毒的攻击，表明这种M2改变作为减毒突变之一潜在地或并入活流感疫苗中。

项目成果

Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles

• DOI: 10.1128/jvi.76.2.767-773.2002
• 发表时间: 2002-01-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Watanabe, T;Watanabe, S;Kawaoka, Y
• 通讯作者: Kawaoka, Y

Neumann G, Kawaoka Y: "Reverse genetics of influenza virus"Virology. 287. 243-250 (2002)

Neumann G、Kawaoka Y：“流感病毒的反向遗传学”病毒学。

Influenza A virus with defective M2 ion channel activity as a live vaccine.

M2 离子通道活性缺陷的甲型流感病毒作为活疫苗。

• 发表时间: 2002
• 期刊: Virology 299
• 作者: Watanabe T;Watanabe S;Kida H;Kawaoka Y
• 通讯作者: Kawaoka Y

Watanabe T, Watanabe S, Neumann G, Kida H, Kawaoka Y: "Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles"Journal of Virology. 76. 767-773 (2002)

Watanabe T、Watanabe S、Neumann G、Kida H、Kawaoka Y：“复制无能流感病毒样颗粒的免疫原性和保护功效”病毒学杂志。

Neumann G, Whitt MA, Kawaoka Y: "A Decade After the Generation of a Negative-Sense RNA Virus From Cloned cDNA-What Have We Learned?"Journal of General Virology. 83. 2635-2662 (2002)

Neumann G、Whitt MA、Kawaoka Y：“从克隆的 cDNA 产生负义 RNA 病毒十年后，我们学到了什么？”普通病毒学杂志。