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Abstract：
The highly conserved extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is a promising target for the development of broad-spectrum vaccines. However, M2e is a poor immunogen by itself and must be linked to an appropriate carrier to induce an efficient immune response. In this study, we obtained recombinant mosaic proteins containing tandem copies of M2e fused to a lipopeptide from Neisseria meningitidis surface lipoprotein Ag473 and alpha-helical linkers and analyzed their immunogenicity. Six fusion proteins, comprising four or eight tandem copies of M2e flanked by alpha-helical linkers, lipopeptides, or a combination of both of these elements, were produced in Escherichia coli. The proteins, containing both alpha-helical linkers and lipopeptides at each side of M2e repeats, formed nanosized particles, but no particulate structures were observed in the absence of lipopeptides. Animal study results showed that proteins with lipopeptides induced strong M2e-specific antibody responses in the absence of external adjuvants compared to similar proteins without lipopeptides. Thus, the recombinant M2e-based proteins containing alpha-helical linkers and N. meningitidis lipopeptide sequences at the N- and C-termini of four or eight tandem copies of M2e peptide are promising vaccine candidates.
摘要：
甲型流感病毒跨膜蛋白M2(M2e)的胞外结构域高度保守是开发广谱疫苗的有希望的靶标。然而,M2e本身是差的免疫原,并且必须与适当的载体连接以诱导有效的免疫应答。在这项研究中,我们获得了含有串联拷贝的M2e与脑膜炎奈瑟球菌表面脂蛋白Ag473的脂肽和α-螺旋接头融合的重组镶嵌蛋白,并分析了它们的免疫原性.六种融合蛋白,包含四个或八个串联拷贝的M2e，两侧是α-螺旋接头，脂肽，或者这两个元素的组合，在大肠杆菌中产生。蛋白质，在M2e重复的每一侧都含有α-螺旋接头和脂肽，形成纳米颗粒，但是在不存在脂肽的情况下没有观察到颗粒结构。动物研究结果显示,与不含脂肽的类似蛋白质相比,在不存在外部佐剂的情况下,具有脂肽的蛋白质诱导强M2e特异性抗体应答。因此，在四个或八个串联拷贝的M2e肽的N-和C-末端含有α-螺旋接头和脑膜炎奈瑟球菌脂肽序列的重组M2e蛋白是有前景的疫苗候选物.
