Monomeric M2e antigen in VesiVax® liposomes stimulates protection against type a strains of influenza comparable to liposomes with multimeric forms of M2e
Monomeric M2e antigen in VesiVax® liposomes stimulates protection against type a strains of influenza comparable to liposomes with multimeric forms of M2e
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DOI：
10.1080/08982104.2017.1381708
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Fujii, G.
中科院分区：
文献类型：
--
作者：
Adler-Moore, J. P.;Ernst, W.;Fujii, G.
考虑到对基质2（M2 e）通道蛋白的胞外域作为开发通用流感疫苗的靶标的兴趣，我们检查了M2 e的抗原构型在产生保护性免疫应答中的作用。制备了一系列M2 e突变和截短的M2 e片段，作为控制M2 e单体、二聚体和更高级多聚体形式形成的手段。将这些M2 e肽中的每一种掺入基于脂质体的疫苗技术平台中，该技术平台先前显示使用M2 e作为单体、二聚体和多聚体的混合物（L-M2 e1-HD/MPL）刺激对甲型流感感染的保护性应答。我们的结果使用这些修饰形式的M2 e在用H1N1（A/PR/8/34）致死性攻击后，在用脂质体中的截短单体形式的M2蛋白M2 e（1-15）接种的近交系BALB/c和远交系瑞士韦伯斯特小鼠中产生90-100%的存活率。这些观察结果表明，当M2 e抗原配制在免疫原性脂质体中时，不需要四聚体构型来引发显著的保护，并且进一步地，M2 e的前15个氨基酸可能在提供保护性免疫应答中起主要作用。
Given the interest in the ectodomain of the matrix 2 (M2e) channel protein as a target for development of a universal influenza vaccine, we examined the role of the antigen configuration of M2e in generating a protective immune response. A series of M2e mutations and a truncated M2e segment were prepared as a means of controlling the formation of monomer, dimer, and higher order multimeric forms of M2e. Each of these M2e peptides was incorporated into a liposome-based vaccine technology platform previously shown to stimulate a protective response to influenza A infection using M2e as a mixture of monomers, dimers and multimers (L-M2e1-HD/MPL). Our results using these modified forms of M2e produced 90-100% survival following lethal challenge with H1N1 (A/PR/8/34) in both inbred BALB/c and outbred Swiss Webster mice vaccinated with a truncated monomeric form of the M2 protein, M2e(1-15) in liposomes. These observations show that a tetrameric configuration is not required to elicit significant protection when the M2e antigen is formulated in immunogenic liposomes and further, that the first 15 amino acids of M2e likely play a primary role in providing the protective immune response.