Influenza Neuraminidase as a Vaccine Antigen
Influenza Neuraminidase as a Vaccine Antigen
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DOI：
10.1007/978-3-540-92165-3_12
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Suarez, David L.
中科院分区：
文献类型：
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作者：
Sylte, Matthew J.;Suarez, David L.
流感病毒的神经氨酸酶蛋白是一种表面糖蛋白，其显示酶活性以从病毒和宿主蛋白中去除唾液酸（病毒受体）。从病毒蛋白中去除唾液酸通过防止血凝素蛋白与其他病毒蛋白结合而聚集病毒，在病毒从细胞中释放中起关键作用。在动物攻击研究中，神经氨酸酶蛋白的抗体可以单独具有保护性，但神经氨酸酶抗体似乎以与血凝素蛋白的抗体不同的方式提供保护。血凝素蛋白的中和抗体可以直接阻断病毒进入，但神经氨酸酶蛋白的保护性抗体被认为主要是将病毒聚集在细胞表面，有效地减少从感染细胞释放的病毒量。神经氨酸酶蛋白可分为九种不同的抗原亚型，其中亚型之间几乎没有抗体的交叉保护。所有九种亚型的神经氨酸酶蛋白通常在禽流感病毒中发现，但只有选定的亚型通常在哺乳动物流感病毒中发现;例如，只有N1和N2亚型通常在人类和猪中发现。即使在亚型内，神经氨酸酶蛋白也可能具有高水平的抗原漂移，并且疫苗接种必须特异性地针对循环菌株以提供最佳保护。神经氨酸酶抗体的水平似乎对于保护也至关重要，人们担心人类流感疫苗不包含足够的神经氨酸酶蛋白来诱导强烈的保护性抗体反应。神经氨酸酶蛋白也已成为靶向唾液酸结合的抗病毒药物的重要靶标，唾液酸结合阻断神经氨酸酶活性。两种不同的抗病毒药物是可用的，并广泛用于治疗人类的季节性流感，但抗病毒药物耐药性似乎是这类抗病毒药物日益关注的问题。
The neuraminidase protein of influenza viruses is a surface glycoprotein that shows enzymatic activity to remove sialic acid, the viral receptor, from both viral and host proteins. The removal of sialic acid from viral proteins plays a key role in the release of the virus from the cell by preventing the aggregation of the virus by the hemagglutinin protein binding to other viral proteins. Antibodies to the neuraminidase protein can be protective alone in animal challenge studies, but the neuraminidase antibodies appear to provide protection in a different manner than antibodies to the hemagglutinin protein. Neutralizing antibodies to the hemagglutinin protein can directly block virus entry, but protective antibodies to the neuraminidase protein are thought to primarily aggregate virus on the cell surface, effectively reducing the amount of virus released from infected cells. The neuraminidase protein can be divided into nine distinct antigenic subtypes, where there is little cross-protection of antibodies between subtypes. All nine subtypes of neuraminidase protein are commonly found in avian influenza viruses, but only selected subtypes are routinely found in mammalian influenza viruses; for example, only the N1 and N2 subtypes are commonly found in both humans and swine. Even within a subtype, the neuraminidase protein can have a high level of antigenic drift, and vaccination has to specifically be targeted to the circulating strain to give optimal protection. The levels of neuraminidase antibody also appear to be critical for protection, and there is concern that human influenza vaccines do not include enough neuraminidase protein to induce a strong protective antibody response. The neuraminidase protein has also become an important target for antiviral drugs that target sialic acid binding which blocks neuraminidase enzyme activity. Two different antiviral drugs are available and are widely used for the treatment of seasonal influenza in humans, but antiviral resistance appears to be a growing concern for this class of antivirals.