Monoclonal antibodies recognizing EVETPIRN epitope of influenza A virus M2 protein could protect mice from lethal influenza A virus challenge
Monoclonal antibodies recognizing EVETPIRN epitope of influenza A virus M2 protein could protect mice from lethal influenza A virus challenge
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DOI：
10.1016/j.imlet.2004.03.003
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发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Chen, YH
中科院分区：
文献类型：
--
作者：
Liu, WL;Zou, P;Chen, YH
基于M2蛋白的24个氨基酸胞外结构域（M2 e）在所有甲型流感病毒株中几乎不变的事实，其他人和我们已经开发了几种不同的M2 e疫苗构建体和疫苗接种方式。虽然这些疫苗在小鼠模型中可以诱导有效的广谱免疫抑制甲型流感病毒感染，但M2 e上的精细保护性表位的信息很少。本文报道了两株M2 e特异性单克隆抗体（mAb）的体内保护性免疫试验，其被动给药对流感病毒A/PR/8/34的5个半数致死量（LD_（50））攻击的保护率为75%。此外，腹腔被动给药12 h后，可在小鼠血清中检测到较高的M2 e特异性抗体滴度（超过1：1600）。肽图分析表明，两株单抗均与M2 e的N端和中间肽段（NM 2，aa 2 -12; MM 2，aa 8 -18）有较强的相互作用，而与C端肽段（CM 2，aa 13 -24）无相互作用。更重要的是，M2 e特异性mAb可识别EVETPIRN（aa 6 -13）肽，该肽是NM 2和MM 2肽的重叠区域及其邻近的氨基酸残基。相反，缺失了EVETPIR序列的M2 e结构域在免疫印迹分析中不能被任一mAb识别。这些结果表明，M2 e上的表位EVETPIRN（aa 6 -13）可能是诱导保护性免疫的原因。(C)2004 Elsevier B. V.保留所有权利。
Based on the fact that the 24 amino acid extracellular domain of M2 protein (M2e) is nearly invariant in all influenza A strains, several different M2e vaccine constructs and vaccination modalities have been developed by others and us. Although most of these vaccines could induce efficient and broad-spectrum immunity inhibiting influenza A virus infection in mice model, information of the refined protective epitope on M2e was scarce. In this paper, two M2e specific monoclonal antibodies (mAbs) conferring protective immunity in vivo were reported, which in passive administration could protect 75% mice from five LD50 (50% lethal dose) challenge of influenza virus A/PR/8/34. In addition, higher M2e specific antibody titer (over 1: 1600) could be detected after 12 h of intraperitoneal passive administration in mice sera. Peptide mapping assay indicated that both mAbs strongly interacted with N-terminus and middle part peptides of M2e (NM2, aa2-12; MM2, aa8-18), but not with the C-terminus peptide (CM2, aa13-24). More importantly, M2e specific mAbs could recognize EVETPIRN (aa6-13) peptide, which were the overlapping region of NM2 and MM2 peptide and the neighboring amino acid residues. In contrast, M2e domain that was deleted EVETPIR sequence could not be recognized by either mAb in immunoblotting assay. All these results indicated that the epitope EVETPIRN (aa6-13) on M2e could be responsible for the induction of the protective immunity. (C) 2004 Elsevier B.V. All rights reserved.