Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans
Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans
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广泛抑制三价流感疫苗和人 H7N9 感染诱导的抗神经氨酸酶单克隆抗体
DOI：
10.1101/682450
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Rijal P
中科院分区：
文献类型：
--
作者：
Rijal P
流感神经氨酸酶（NA）诱导的大多数抗体，如抗血凝素（HA）的抗体，对有限时间窗内分离的病毒具有相对特异性，如血清学研究和许多鼠单克隆抗体（MAb）分析所示。我们报告了三个广泛反应的人单克隆抗体靶向N1 NA。两个分离自接种三价流感疫苗（TIV）的年轻成人，三价流感疫苗（TIV）在一百年的时间内抑制从人分离的病毒的N1 NA。从患有急性轻度H7N9感染的儿童中分离的第三种抗体抑制第1组N1和第2组N9 NA。此外，抗体交叉抑制高致病性禽H5N1流感病毒的N1 NA。这些抗体在预防小鼠感染季节性H1N1病毒方面具有保护作用。这项研究表明，具有特殊交叉反应性的N1 NA的人抗体可以通过疫苗接种被召回，并强调了在季节性疫苗中标准化NA抗原以提供最佳保护的重要性。重要信息流感病毒NA的抗体可以提供针对流感疾病的保护。人NA抗体的分析落后于HA抗体的分析。我们发现，由疫苗接种和感染诱导的针对NA的人单克隆抗体可以具有非常广泛的反应性，能够抑制1918年至2018年之间分离的病毒上的广谱N1 NA。这表明NA抗体可能是一种有用的治疗方法，并且流感疫苗的功效可以通过确保NA抗原的适当含量来增强。
The majority of antibodies induced by influenza neuraminidase (NA), like those against hemagglutinin (HA), are relatively specific to viruses isolated within a limited time window, as seen in serological studies and the analysis of many murine monoclonal antibodies (MAbs). We report three broadly reactive human MAbs targeting N1 NA. Two were isolated from a young adult vaccinated with trivalent influenza vaccine (TIV), which inhibited N1 NA from viruses isolated from humans over a period of a hundred years. The third antibody, isolated from a child with acute mild H7N9 infection, inhibited both group 1 N1 and group 2 N9 NAs. In addition, the antibodies cross-inhibited the N1 NAs of highly pathogenic avian H5N1 influenza viruses. These antibodies are protective in prophylaxis against seasonal H1N1 viruses in mice. This study demonstrates that human antibodies to N1 NA with exceptional cross-reactivity can be recalled by vaccination and highlights the importance of standardizing the NA antigen in seasonal vaccines to offer optimal protection.IMPORTANCEAntibodies to the influenza virus NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that of antibodies to HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive, with the ability to inhibit a wide spectrum of N1 NAs on viruses isolated between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy and that the efficacy of influenza vaccines could be enhanced by ensuring the appropriate content of NA antigen.