Novel correlates of protection against pandemic H1N1 influenza A virus infection
Novel correlates of protection against pandemic H1N1 influenza A virus infection
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DOI：
10.1038/s41591-019-0463-x
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发表时间：
2019-06-01
期刊：
影响因子：
82.9
通讯作者：
Gordon, Aubree
中科院分区：
文献类型：
--
作者：
Ng, Sophia;Nachbagauer, Raffael;Gordon, Aubree
流感病毒仍然是人类健康的严重威胁，每年造成多达650，000人死亡（1，2）。季节性流感病毒疫苗可以预防感染，但由于抗原漂移而无效。为了提供更好的感染保护，目前正在开发靶向流感病毒保守表位的新型流感病毒疫苗，特别是血凝素茎和神经氨酸酶中的那些。抗血凝素茎的抗体在动物研究中提供保护（4-6）。然而，没有关于人类自然感染的数据，并且这些抗体在血凝抑制试验中未显示活性，血凝抑制滴度是目前与预防流感病毒感染相关的（7-9）。虽然先前的研究已经调查了细胞免疫应答和神经氨酸酶抑制抗体的保护作用，但是保护免受感染的其他血清学相关性可以帮助开发广泛保护性或通用流感病毒疫苗（10-13）。为了解决这一差距，我们进行了一项家庭传播研究，以确定保护自然暴露个体免受感染和疾病的替代相关性。利用这项研究，我们确定了50%的保护滴度和水平的血凝抑制，全长血凝素，神经氨酸酶和血凝素茎特异性抗体。此外，我们发现血凝素茎抗体与流感病毒感染的保护作用独立相关。
Influenza viruses remain a severe threat to human health, causing up to 650,000 deaths annually(1,2). Seasonal influenza virus vaccines can prevent infection, but are rendered ineffective by antigenic drift. To provide improved protection from infection, novel influenza virus vaccines that target the conserved epitopes of influenza viruses, specifically those in the hemagglutinin stalk and neuraminidase, are currently being developed3. Antibodies against the hemagglutinin stalk confer protection in animal studies(4-6). However, no data exist on natural infections in humans, and these antibodies do not show activity in the hemagglutination inhibition assay, the hemagglutination inhibition titer being the current correlate of protection against influenza virus infection(7-9). While previous studies have investigated the protective effect of cellular immune responses and neuraminidase-inhibiting antibodies, additional serological correlates of protection from infection could aid the development of broadly protective or universal influenza virus vaccines(10-13). To address this gap, we performed a household transmission study to identify alternative correlates of protection from infection and disease in naturally exposed individuals. Using this study, we determined 50% protective titers and levels for hemagglutination inhibition, full-length hemagglutinin, neuraminidase and hemagglutinin stalk-specific antibodies. Further, we found that hemagglutinin stalk antibodies independently correlated with protection from influenza virus infection.