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H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix vaccination

机译:H1N1病毒蛋白质组肽微阵列可预测有H1N1感染风险的人并与Pandemrix疫苗接种相比隔离感染

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A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix((R)) vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251-265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.
机译:高含量的肽微阵列,包含整个甲型流感病毒[A / California / 08/2009(H1N1)]蛋白质组和来自其他12种甲型流感的亚型的血凝素蛋白,包括来自[A / South Carolina / 1/1918(H1N1)的血凝素)]菌株用于在2009年大流行性流感季节期间在瑞典队列中进行Pandemrix(R)疫苗接种或H1N1感染之前和之后测量血清IgG表位特征。观察到非常窄的大流行性流感特异性IgG表位识别模式后来感染H1N1感染者的血清中的血红蛋白水平升高。此外,大流行性流感感染产生了与神经氨酸酶蛋白的两个相邻表位的IgG反应性。差异的血清IgG识别集中在血凝素1(H1)上,并且在接种疫苗的对照和患有流感感染的个体中都局限于经典抗原位点(Cb)。我们进一步在大流行性流感血凝素的Ca抗原位点(251-265)上确定了一个新的抗原决定簇VEPGDKITFEATGNL,该抗原表位仅在先前接种疫苗的个体的血清中被识别,而从未在H1N1感染者的血清中被识别(通过RNA PCR分析证实)鼻拭子)。该表位被定位到流感血凝素的受体结合结构域,在大流行性流感的情况下可以作为免疫保护的相关物质。研究表明,使用肽微阵列技术进行无偏见的表位作图可以鉴定生物学和临床上相关的靶标结构。与大流行的H1N1疫苗相比,H1N1感染最明显地诱导了IgG表位识别模式的不同足迹。

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