Center for Research on Influenza Pathogenesis (CRIP), New York, New York, USA
Icahn School of Medicine at Mount Sinai, New York, New York, USA.
mBio. 2018 Apr 3;9(2):e02332-17. doi: 10.1128/mBio.02332-17.
Neuraminidase is one of the two surface glycoproteins of influenza A and B viruses. It has enzymatic activity that cleaves terminal sialic acid from glycans, and that activity is essential at several points in the virus life cycle. While neuraminidase is a major target for influenza antivirals, it is largely ignored in vaccine development. Current inactivated influenza virus vaccines might contain neuraminidase, but the antigen quantity and quality are varied and not standardized. While there are data that show a protective role of anti-neuraminidase immunity, many questions remain unanswered. These questions, among others, concern the targeted epitopes or antigenic sites, the potential for antigenic drift, and, connected to that, the breadth of protection, differences in induction of immune responses by vaccination versus infection, mechanisms of protection, the role of mucosal antineuraminidase antibodies, stability, and the immunogenicity of neuraminidase in vaccine formulations. Reagents for analysis of neuraminidase-based immunity are scarce, and assays are not widely used for clinical studies evaluating vaccines. However, efforts to better understand neuraminidase-based immunity have been made recently. A neuraminidase focus group, NAction!, was formed at a Centers of Excellence for Influenza Research and Surveillance meeting at the National Institutes of Health in Bethesda, MD, to promote research that helps to understand neuraminidase-based immunity and how it can contribute to the design of better and broadly protective influenza virus vaccines. Here, we review open questions and knowledge gaps that have been identified by this group and discuss how the gaps can be addressed, with the ultimate goal of designing better influenza virus vaccines.
神经氨酸酶是甲型和乙型流感病毒的两种表面糖蛋白之一。它具有酶活性，可从聚糖中切割末端唾液酸，该活性在病毒生命周期的几个关键点是必不可少的。虽然神经氨酸酶是流感抗病毒药物的主要靶标，但在疫苗开发中基本上被忽略了。目前的灭活流感病毒疫苗可能含有神经氨酸酶，但抗原数量和质量各不相同且未标准化。虽然有数据表明抗神经氨酸酶免疫具有保护作用，但仍有许多问题尚未得到解答。这些问题包括针对特定表位或抗原位点、潜在的抗原漂移、以及与之相关的保护范围、接种与感染引起的免疫反应的差异、保护机制、粘膜抗神经氨酸酶抗体的作用、稳定性以及疫苗配方中神经氨酸酶的免疫原性。用于分析基于神经氨酸酶的免疫的试剂稀缺，并且该测定法未广泛用于评估疫苗的临床研究。然而，最近已经做出了努力以更好地了解基于神经氨酸酶的免疫。在马里兰州贝塞斯达的美国国立卫生研究院举行的流感研究与监测卓越中心会议上成立了一个神经氨酸酶焦点小组 NAction！，以促进有助于了解基于神经氨酸酶的免疫以及它如何为设计更好和广泛保护的流感病毒疫苗做出贡献的研究。在这里，我们回顾了该小组确定的悬而未决的问题和知识空白，并讨论了如何解决这些空白，最终目标是设计更好的流感病毒疫苗。
