Assessing the Protective Potential of H1N1 Influenza Virus Hemagglutinin Head and Stalk Antibodies in Humans
Assessing the Protective Potential of H1N1 Influenza Virus Hemagglutinin Head and Stalk Antibodies in Humans
复制标题
DOI：
10.1128/jvi.02134-18
复制
发表时间：
2019-04-01
影响因子：
5.4
通讯作者：
Hensley, Scott E.
中科院分区：
文献类型：
--
作者：
Christensen, Shannon R.;Toulmin, Sushila A.;Hensley, Scott E.
季节性流感病毒是全球人类疾病的主要原因。大多数由流感病毒引发的中和抗体（Ab）靶向血凝素（HA）蛋白的头部结构域。抗HA头部Ab可以是高度有效的，但它们具有有限的宽度，因为HA头部是可变的。人们对开发新的普遍免疫策略产生了极大的兴趣，这些策略可以引发针对HA保守区域（如茎域）的广泛中和抗体。尽管HA茎抗体可以在动物模型中提供保护，但尚不清楚它们是否以足够的水平存在于人类中以提供针对天然获得性流感病毒感染的保护。在这里，我们量化了2015-2016年流感病毒季节期间住院的179名成年人的H1N1 HA头部和茎特异性抗体。我们发现，HA头抗体，血凝素抑制（HAI）测定，与自然获得性H1N1感染的保护。HA茎特异性血清总IgG滴度也与保护相关，但这种相关性减弱，并且在调整HA头特异性Ab滴度后不具有统计学显著性。我们发现HA茎特异性IgG 1和伊加抗体在未感染的参与者血清中的滴度略高于感染的参与者血清中的滴度;然而，我们发现血清体外抗体依赖性细胞毒性活性无差异。在被动转移实验中，来自具有高HAI活性的参与者的血清有效地保护小鼠，而具有低HAI活性的血清保护小鼠的程度较低。我们的数据表明，HA头部抗体是更有效地保护免受H1N1感染比HA茎Abs.IMPORTANCE抗体针对流感病毒的HA头部通常与流感病毒感染的保护。这些Ab通常具有有限的宽度，因为突变经常出现在HA头部表位中。靶向更保守的HA茎域的新疫苗正在开发中。靶向HA茎的Ab在动物模型中具有保护性，但尚不清楚这些Ab是否以保护水平存在于人类中。在这里，我们完成了实验，以确定在2015-2016年流感季节期间，针对HA头部和茎部的Ab是否与保护免受自然获得的人类流感病毒感染相关。
Seasonal influenza viruses are a major cause of human disease worldwide. Most neutralizing antibodies (Abs) elicited by influenza viruses target the head domain of the hemagglutinin (HA) protein. Anti-HA head Abs can be highly potent, but they have limited breadth since the HA head is variable. There is great interest in developing new universal immunization strategies that elicit broadly neutralizing Abs against conserved regions of HA, such as the stalk domain. Although HA stalk Abs can provide protection in animal models, it is unknown if they are present at sufficient levels in humans to provide protection against naturally acquired influenza virus infections. Here, we quantified H1N1 HA head- and stalk-specific Abs in 179 adults hospitalized during the 2015-2016 influenza virus season. We found that HA head Abs, as measured by hemagglutinin inhibition (HAI) assays, were associated with protection against naturally acquired H1N1 infection. HA stalk-specific serum total IgG titers were also associated with protection, but this association was attenuated and not statistically significant after adjustment for HA head- specific Ab titers. We found slightly higher titers of HA stalk-specific IgG1 and IgA Abs in sera from uninfected participants than in sera from infected participants; however, we found no difference in serum in vitro antibody-dependent cellular cytotoxicity activity. In passive transfer experiments, sera from participants with high HAI activity efficiently protected mice, while sera with low HAI activity protected mice to a lower extent. Our data suggest that HA head Abs are more efficient at protecting against H1N1 infection than HA stalk Abs.IMPORTANCE Abs targeting the HA head of influenza viruses are often associated with protection from influenza virus infections. These Abs typically have limited breadth, since mutations frequently arise in HA head epitopes. New vaccines targeting the more conserved HA stalk domain are being developed. Abs that target the HA stalk are protective in animal models, but it is unknown if these Abs exist at protective levels in humans. Here, we completed experiments to determine if Abs against the HA head and stalk were associated with protection from naturally acquired human influenza virus infections during the 2015-2016 influenza season.