A universal influenza A vaccine based on the extracellular domain of the M2 protein

A universal influenza A vaccine based on the extracellular domain of the M2 protein
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DOI:
10.1038/13484
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发表时间:
1999-10-01
期刊:
影响因子:
82.9
通讯作者:
Fiers, W
Fiers, W
中科院分区:
医学1区
文献类型:
--
作者:
Neirynck, S;Deroo, T;Fiers, W

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流感病毒的抗原变异是一个主要的健康问题。然而,在所有甲型流感毒株中,由病毒编码的次要蛋白M2的胞外结构域几乎是不变的。我们将这个M2结构域与乙肝病毒核心(HBc)蛋白进行基因融合,构建了编码M2HBc的融合基因;该基因在大肠杆菌中高效表达。给小鼠腹腔内或鼻腔内施用纯化的M2HBc颗粒,可使其在致命的病毒攻击下获得90 - 100%的保护率。这种保护是由抗体介导的,因为它可通过血清转移。暴露在HBc颗粒上的M2胞外结构域免疫原性增强,可针对甲型流感感染提供广谱、持久的保护。
The antigenic variation of influenza virus represents a major health problem. However, the extracellular domain of the minor, virus-coded M2 protein is nearly invariant in all influenza A strains. We genetically fused this M2 domain to the hepatitis B virus core (HBc) protein to create fusion gene coding for M2HBc; this gene was efficiently expressed in Escherichia coli. Intraperitoneal or intranasal administration of purified M2HBc particles to mice provided 90-100% protection against a lethal virus challenge. The protection was mediated by antibodies, as it was transferable by serum. The enhanced immunogenicity of the M2 extracellular domain exposed on HBc particles allows broad-spectrum, long-lasting protection against influenza A infections.