Characterizations of four monoclonal antibodies against M2 protein ectodomain of influenza A virus
Characterizations of four monoclonal antibodies against M2 protein ectodomain of influenza A virus
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DOI：
10.1016/j.virol.2008.11.035
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发表时间：
2009-03-01
期刊：
影响因子：
3.7
通讯作者：
Liang, Xiaoping
中科院分区：
文献类型：
--
作者：
Fu, Tong-Ming;Freed, Daniel C.;Liang, Xiaoping
甲型流感病毒的M2蛋白已被认为是具有广泛跨毒株覆盖的疫苗的靶标。在小动物模型中的研究表明，由23-mer M2肽疫苗诱导的抗体应答可以提供针对甲型流感病毒攻击的保护。为了研究Merck M2-OMPC结合疫苗的抗病毒机制，我们制备并表征了四种M2肽特异性单克隆抗体（mAb）。在这里，我们证明了我们的M2 mAb的保护作用不依赖于小鼠中NK介导的效应子功能。保护性mAb优先结合由两个或更多个平行取向的M2肽组成的M2多聚体。我们的研究结果表明，保护性M2抗体更喜欢结合位于N-末端10个氨基酸的M2肽的表位，和表位可能是由两个M2肽在平行方向形成。这些结果在抗病毒机制的免疫反应诱导的M2疫苗的影响进行了讨论。(c)2008年爱思唯尔公司All rights reserved.
M2 protein of influenza A virus has been implicated as a target for vaccines with broad cross-strain coverage. Studies in small animal models have shown that antibody responses induced by 23-mer M2 peptide vaccines can provide protection against influenza A virus challenge. To study antiviral mechanisms of Merck M2-OMPC conjugate vaccine, we generated and characterized four M2 peptide-specific monoclonal antibodies (mAbs). Here we demonstrated that the protection by our M2 mAbs is independent of NK-mediated effector functions in mice. The protective mAbs preferentially bind to M2 multimers composed of two or more M2 peptides in parallel orientation. Our findings indicate that the protective M2 Ab prefer to bind to epitopes located within the N-terminal 10 amino acids of the M2 peptide, and the epitopes are likely formed by two M2 peptides in parallel orientation. The implications of these results in antiviral mechanisms of immune responses induced by M2 vaccines are discussed. (c) 2008 Elsevier Inc. All rights reserved.