Human Monoclonal Antibodies to Pandemic 1957 H2N2 and Pandemic 1968 H3N2 Influenza Viruses
Human Monoclonal Antibodies to Pandemic 1957 H2N2 and Pandemic 1968 H3N2 Influenza Viruses
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DOI：
10.1128/jvi.07158-11
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发表时间：
2012-06-01
影响因子：
5.4
通讯作者：
Crowe, James E., Jr.
中科院分区：
文献类型：
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作者：
Krause, Jens C.;Tsibane, Tshidi;Crowe, James E., Jr.
对1957年甲型流感大流行H2N2病毒的人类抗体反应的调查主要局限于血清学研究。我们利用杂交瘤技术从1950年至1968年间出生的健康献血者的外周血中产生了5种流感病毒血凝素（HA）反应性人单克隆抗体（mab）。两种单克隆抗体与大流行H2N2病毒反应，两种识别大流行H3N2病毒，值得注意的是，一种单克隆抗体同时与大流行H2N2和H3N2病毒反应。这五种自然产生的单克隆抗体均表现出血凝抑制活性，表明对流感病毒HA的球状头结构域具有特异性。当与病毒孵育时，单克隆抗体8F8、8M2和2G1分别在胚性鸡蛋HA球形头部的受体结合域附近引发H2N2逃逸突变。所有h2n2特异性单克隆抗体都能抑制2006年猪H2N3流感病毒。单克隆抗体8M2和2G1共享V(H)1-69种系基因，但这些抗体在其他方面没有遗传相关性。每种抗体都能在致命的H2N2病毒攻击中保护小鼠。因此，即使在H2N2病毒循环43年后，这些受试者的外周血B细胞仍具有编码对大流行H2 HA球形头部保守区域特异性的强效抑制抗体。
Investigation of the human antibody response to the 1957 pandemic H2N2 influenza A virus has been largely limited to serologic studies. We generated five influenza virus hemagglutinin (HA)-reactive human monoclonal antibodies (MAbs) by hybridoma technology from the peripheral blood of healthy donors who were born between 1950 and 1968. Two MAbs reacted with the pandemic H2N2 virus, two recognized the pandemic H3N2 virus, and remarkably, one reacted with both the pandemic H2N2 and H3N2 viruses. Each of these five naturally occurring MAbs displayed hemagglutination inhibition activity, suggesting specificity for the globular head domain of influenza virus HA. When incubated with virus, MAbs 8F8, 8M2, and 2G1 each elicited H2N2 escape mutations immediately adjacent to the receptor-binding domain on the HA globular head in embryonated chicken eggs. All H2N2-specific MAbs were able to inhibit a 2006 swine H2N3 influenza virus. MAbs 8M2 and 2G1 shared the V(H)1-69 germ line gene, but these antibodies were otherwise not genetically related. Each antibody was able to protect mice in a lethal H2N2 virus challenge. Thus, even 43 years after circulation of H2N2 viruses, these subjects possessed peripheral blood B cells encoding potent inhibiting antibodies specific for a conserved region on the globular head of the pandemic H2 HA.