Pseudotype-based neutralization assays for influenza: a systematic analysis.
Pseudotype-based neutralization assays for influenza: a systematic analysis.
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DOI：
10.3389/fimmu.2015.00161
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发表时间：
2015
影响因子：
7.3
通讯作者：
Temperton NJ
中科院分区：
文献类型：
--
作者：
Carnell GW;Ferrara F;Grehan K;Thompson CP;Temperton NJ
使用针对流感病毒的疫苗仍然是减轻该病毒引起的严重发病率和死亡率的最有效方法。由目前许可的流感疫苗引发的抗体主要是具有血凝抑制（HI）能力的抗体，其靶向血凝素（HA）的球状头部，从而抑制流感病毒进入靶细胞。这些抗体主要赋予同源亚型/菌株特异性保护，仅很少赋予异源亚型保护。然而，最近学术界或制药公司领导的生产“通用疫苗”的研发集中在诱导针对流感HA茎的抗体上，该抗体已被证明在一系列不同亚型（H1-H16）中提供广泛的保护。然而，这些“下一代”流感疫苗引起的抗体应答的准确和灵敏的测量受到传统流感血清学测定HI、单放射状溶血和微量中和缺乏灵敏度的阻碍。利用假型（携带流感糖蛋白的嵌合病毒）的测定已被证明可高效测量同型和异型广泛中和抗体，使其成为研究针对具有大流行潜力的多种流感亚型的交叉保护性应答的理想血清学工具。在这篇综述中，我们将分析和比较文献涉及生产流感假型，特别强调其在血清抗体中和试验中的使用。这将使我们能够建立优化所需的参数，并提出一个共识协议，用于在流感疫苗免疫原性研究中进一步部署这些检测。
The use of vaccination against the influenza virus remains the most effective method of mitigating the significant morbidity and mortality caused by this virus. Antibodies elicited by currently licensed influenza vaccines are predominantly hemagglutination-inhibition (HI)-competent antibodies that target the globular head of hemagglutinin (HA) thus inhibiting influenza virus entry into target cells. These antibodies predominantly confer homosubtypic/strain specific protection and only rarely confer heterosubtypic protection. However, recent academia or pharma-led R&D toward the production of a “universal vaccine” has centered on the elicitation of antibodies directed against the stalk of the influenza HA that has been shown to confer broad protection across a range of different subtypes (H1–H16). The accurate and sensitive measurement of antibody responses elicited by these “next-generation” influenza vaccines is, however, hampered by the lack of sensitivity of the traditional influenza serological assays HI, single radial hemolysis, and microneutralization. Assays utilizing pseudotypes, chimeric viruses bearing influenza glycoproteins, have been shown to be highly efficient for the measurement of homosubtypic and heterosubtypic broadly neutralizing antibodies, making them ideal serological tools for the study of cross-protective responses against multiple influenza subtypes with pandemic potential. In this review, we will analyze and compare literature involving the production of influenza pseudotypes with particular emphasis on their use in serum antibody neutralization assays. This will enable us to establish the parameters required for optimization and propose a consensus protocol to be employed for the further deployment of these assays in influenza vaccine immunogenicity studies.
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