Wang Sheng-Fan, Tseng Sung-Pin, Loh El-Wui, Wang Wen-Hung, Li Ming-Chun, Chen Kuan-Hsuan, Tsai Wan-Chi, Lee Yuan-Ming, Chen Huan-Yuan, Liu Fu-Tong, Arthur Chen Yi-Ming, Huang Jason C
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Dev Comp Immunol. 2017 Feb;67:8-17. doi: 10.1016/j.dci.2016.10.010. Epub 2016 Oct 27.
In 2009, a swine-origin influenza A virus - A(H1N1)pdm09 - emerged and has became a pandemic strain circulating worldwide. The hemagglutinin (HA) of influenza virus is a potential target for the development of anti-viral therapeutic agents. Here, we generated mAbs by immunization of baculovirus-insect expressing trimeric recombinant HA of the A(H1N1)pdm09 strain. Results indicated that the mAbs recognized two novel neutralizing and protective epitopes-"STAS" and "FRSK" which located near Cb and Ca1 antigenic regions respectively and were conserved in almost 2009-2016 influenza H1N1 stains. The mAb 12E11 demonstrated higher protective efficacy than mAb 8B10 in mice challenge assay. Both mAb pretreatments significantly reduced virus titers and pro-inflammatory cytokines in mice lung postinfection (p < 0.01), and showed prophylactic and therapeutic efficacies even 48 h postinfection (p < 0.05). Combination therapy using the mAbs with oseltamivir pre- and post-treatment showed synergistic therapeutic effect in mice model (p < 0.01). Further investigation for clinical application in humans is warranted.
2009年，一种源自猪的甲型流感病毒——甲型H1N1流感病毒（A(H1N1)pdm09）出现，并成为在全球传播的大流行毒株。流感病毒的血凝素（HA）是开发抗病毒治疗药物的潜在靶点。在此，我们通过用杆状病毒-昆虫表达的A(H1N1)pdm09毒株三聚体重组HA进行免疫来制备单克隆抗体（mAb）。结果表明，这些单克隆抗体识别出两个新的中和及保护性表位——“STAS”和“FRSK”，它们分别位于Cb和Ca1抗原区附近，并且在2009 - 2016年的几乎所有甲型H1N1流感毒株中都保守存在。在小鼠攻毒试验中，单克隆抗体12E11显示出比单克隆抗体8B10更高的保护效力。两种单克隆抗体预处理均显著降低了感染后小鼠肺内的病毒滴度和促炎细胞因子水平（p < 0.01），并且即使在感染后48小时仍显示出预防和治疗效果（p < 0.05）。在小鼠模型中，单克隆抗体与奥司他韦联合进行治疗前和治疗后的联合疗法显示出协同治疗效果（p < 0.01）。有必要进一步研究其在人类中的临床应用。
