A Pan-H1 Anti-Hemagglutinin Monoclonal Antibody with Potent Broad-Spectrum Efficacy In Vivo
A Pan-H1 Anti-Hemagglutinin Monoclonal Antibody with Potent Broad-Spectrum Efficacy In Vivo
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DOI：
10.1128/jvi.00469-12
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发表时间：
2012-06-01
影响因子：
5.4
通讯作者：
Palese, Peter
中科院分区：
文献类型：
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作者：
Tan, Gene S.;Krammer, Florian;Palese, Peter
由甲型流感病毒抗原变异引起的季节性流行病仍然是一个公共卫生问题和经济负担。广泛中和的抗血凝素单克隆抗体（MAb）的分离和表征突出了不同甲型流感病毒中高度保守表位的存在。在这里，我们描述了一种小鼠单克隆抗体的生成和表征，该抗体旨在靶向甲型流感H1病毒的血凝素的保守区域，甲型流感H1病毒是一种在20世纪和21世纪引起人类大流行的亚型。通过用编码抗原性不同的Hl甲型流感病毒（A/南卡罗来纳州/1/1918、A/USSR/92/1977和A/加州/4/2009）的血凝素的质粒DNA顺序免疫小鼠，我们分离并鉴定了MAb 6 F12。与先前描述的其他广泛中和MAb相似，MAb 6 F12对甲型流感病毒没有血凝抑制活性，并且靶向血凝素的茎区。按照设计，它在体外对一组不同的H1病毒具有中和活性，代表了79年的抗原漂移。最值得注意的是，MAb 6 F12在小鼠被动转移实验中，无论是在暴露前还是暴露后预防方案中，都能预防针对不同H1病毒的总体重减轻。MAb 6 F12的广泛但特异的活性突出了单克隆抗体针对甲型流感病毒单一亚型的有效性。
Seasonal epidemics caused by antigenic variations in influenza A virus remain a public health concern and an economic burden. The isolation and characterization of broadly neutralizing anti-hemagglutinin monoclonal antibodies (MAb) have highlighted the presence of highly conserved epitopes in divergent influenza A viruses. Here, we describe the generation and characterization of a mouse monoclonal antibody designed to target the conserved regions of the hemagglutinin of influenza A H1 viruses, a subtype that has caused pandemics in the human population in both the 20th and 21st centuries. By sequentially immunizing mice with plasmid DNA encoding the hemagglutinin of antigenically different HI influenza A viruses (A/South Carolina/1/1918, A/USSR/92/1977, and A/California/4/2009), we isolated and identified MAb 6F12. Similar to other broadly neutralizing MAb previously described, MAb 6F12 has no hemagglutination inhibition activity against influenza A viruses and targets the stalk region of hemagglutinins. As designed, it has neutralizing activity against a divergent panel of H1 viruses in vitro, representing 79 years of antigenic drift. Most notably, MAb 6F12 prevented gross weight loss against divergent H1 viruses in passive transfer experiments in mice, both in pre- and postexposure prophylaxis regimens. The broad but specific activity of MAb 6F12 highlights the potent efficacy of monoclonal antibodies directed against a single subtype of influenza A virus.