Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1 influenza A virus in vitro and in vivo
Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1 influenza A virus in vitro and in vivo
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DOI：
10.1007/s00705-013-1852-y
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发表时间：
2014-03-01
影响因子：
2.7
通讯作者：
Chen, Ze
中科院分区：
文献类型：
--
作者：
Chen, Jianjun;Yan, Bin;Chen, Ze
2009年甲型流感大流行病毒（H1N1）对全球公共卫生构成严重挑战。为了表征该病毒的中和性表位，我们生成了8个单克隆抗体（mab），用于抗a/ California/07/2009病毒的HA。抗体对2009 pdm H1N1 HA具有特异性，因为抗体显示HA特异性ELISA，血凝抑制（HAI）和中和活性。其中一个单抗（mAb12）的HAI和中和效价明显高于其他单抗。我们通过描述2009年H1N1疫苗株（NYMC X-179A）的逃逸突变体，绘制了HA的抗原表位。氨基酸的变化表明，这8个单抗识别HA抗原表位位于Sa、Sb、Ca1和Ca2位点。单克隆抗体被动免疫表明，mAb12在体内表现出比其他单克隆抗体更有效的中和活性。mAb12还被发现对小鼠的致命病毒攻击具有预防和治疗作用。此外，单次注射10mg /kg mAb12在预防和治疗致命病毒感染方面优于奥司他韦5天疗程（灌胃10mg /kg/天）。综上所述，我们的结果表明，小鼠来源的单克隆抗体在体外和体内都显示出中和效果。其中一个单抗（mAb12）识别了Sb位点内的表位，并表现出出色的中和效果。
Pandemic influenza A virus (H1N1) 2009 poses a serious public-health challenge worldwide. To characterize the neutralizing epitopes of this virus, we generated a panel of eight monoclonal antibodies (mAbs) against the HA of the A/California/07/2009 virus. The antibodies were specific for the 2009 pdm H1N1 HA, as the antibodies displayed HA-specific ELISA, hemagglutination inhibition (HAI) and neutralization activity. One mAb (mAb12) showed significantly higher HAI and neutralizing titers than the other mAbs. We mapped the antigenic epitopes of the HA by characterizing escape mutants of a 2009 H1N1 vaccine strain (NYMC X-179A). The amino acid changes suggested that these eight mAbs recognized HA antigenic epitopes located in the Sa, Sb, Ca1 and Ca2 sites. Passive immunization with mAbs showed that mAb12 displayed more efficient neutralizing activity in vivo than the other mAbs. mAb12 was also found to be protective, both prophylactically and therapeutically, against a lethal viral challenge in mice. In addition, a single injection of 10 mg/kg mAb12 outperformed a 5-day course of treatment with oseltamivir (10 mg/kg/day by gavage) with respect to both prophylaxis and treatment of lethal viral infection. Taken together, our results showed that mouse-origin mAbs displayed neutralizing effectiveness in vitro and in vivo. One mAb in particular (mAb12) recognized an epitope within the Sb site and demonstrated outstanding neutralizing effectiveness.