M2e-based universal influenza A vaccine
M2e-based universal influenza A vaccine
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DOI：
10.1016/j.vaccine.2009.07.007
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发表时间：
2009-10-23
期刊：
影响因子：
5.5
通讯作者：
Saelens, Xavier
中科院分区：
文献类型：
--
作者：
Fiers, Walter;De Filette, Marina;Saelens, Xavier
人类流感导致大量发病率和死亡率。目前，获得许可的流感疫苗如果与感染株相匹配，则可以提供令人满意的保护，但它们也有明显的缺点。这些疫苗源自原型病毒，含有可能引起下一次流行的流感病毒的血凝素。然而，它们对抗未来大流行的有用性仍然存在问题。基于流感基质蛋白 2 (M2e) 胞外域的疫苗可以克服这些缺点。 M2e 在人类和禽甲型流感病毒中都高度保守。通过将 M2e 与适当的载体（例如乙型肝炎病毒衍生的病毒样颗粒）融合，可以克服针对天然 M2e 的低免疫原性。这种嵌合颗粒可以在简单且安全的细菌表达系统中产生，需要最少的生物防护，并且可以以纯净的形式获得。动物模型实验表明，基于 M2e 的疫苗可诱导针对各种甲型流感病毒亚型致命攻击的保护作用。此外，无论季节如何，无论是在流行病还是在大流行防备计划中，都可以随时生产和使用有效的 M2e 疫苗。在动物模型中，经肠胃外或鼻内施用的 M2e 疫苗可以预防各种甲型流感病毒株攻击后的疾病和死亡。适合人类使用的佐剂可改善保护作用，这与特定亚型的较高抗 M2e 抗体反应相关。最近，M2e疫苗的I期临床研究已经完成，表明其安全性和免疫原性。目前正在对这种通用甲型流感候选疫苗进行进一步的临床开发，以验证其对人类的保护功效。 (C) 2009 年，爱思唯尔有限公司出版。
Human influenza causes substantial morbidity and mortality. Currently, licensed influenza vaccines offer satisfactory protection if they match the infecting strain, but they come with significant drawbacks. These vaccines are derived from prototype viruses, containing the hemagglutinin of influenza viruses that are likely to cause the next epidemic. Their usefulness against a future pandemic, however, remains problematic. A vaccine based on the ectodomain of influenza matrix protein 2 (M2e) could overcome these drawbacks. M2e is highly conserved in both human and avian influenza A viruses. The low immunogenicity against natural M2e can be overcome by fusing M2e to an appropriate carrier such as Hepatitis B virus-derived virus-like particles. Such chimeric particles can be produced in a simple and safe bacterial expression system, requiring minimal biocontainment, and can be obtained in a pure form. Experiments in animal models have demonstrated that M2e-based vaccines induce protection against a lethal challenge with various influenza A virus subtypes. Furthermore, the production and use of an effective M2e-vaccine could be implemented at any time regardless of seasonality, both in an epidemic as well as in a pandemic preparedness program. In animal models, M2e-vaccines administered parenterally or intranasally protect against disease and mortality following challenge with various influenza A strains. Adjuvants suitable for human use improve protection, which correlates with higher anti-M2e antibody responses of defined subtypes. Recently, Phase I clinical studies with M2e-vaccines have been completed, indicating their safety and immunogenicity. Further clinical development of this universal influenza A vaccine candidate is being pursued in order to validate its protective efficacy in humans. (C) 2009 Published by Elsevier Ltd.