He Fang, Kwang Jimmy
Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604.
Influenza Res Treat. 2013;2013:360675. doi: 10.1155/2013/360675. Epub 2013 Mar 5.
H5N1 influenza viruses cause high mortality in avian and mammalian species, including humans. Antigenic drift in H5 sequence poses challenges in the development of vaccine and therapeutic antibody. In this study, a monoclonal antibody 11G12 was produced from inactivated H5N1 immunized mice. Results from IFA, ELISA, HI, and virus neutralization indicated that Mab 11G12 can specifically recognize and neutralize H5 type hemagglutinin from clade 1 and 0 without any cross-reaction to any other clades of H5N1 viruses. Mab 11G12 was used to differentiate and quantify the expression of H5N1 strain A/VietNam/1203/04 from a trivalent vaccine mix in ELISA. Sequencing of escape mutants identified that Mab 11G12 targets a major neutralizing epitope of influenza H5 hemagglutinin. The study indicated that some major neutralizing epitopes in H5s of early strains were mutated due to antigenic drift.
H5N1流感病毒在包括人类在内的禽类和哺乳动物物种中会导致高死亡率。H5序列中的抗原漂移给疫苗和治疗性抗体的研发带来了挑战。在本研究中,用灭活的H5N1免疫小鼠制备了单克隆抗体11G12。免疫荧光分析(IFA)、酶联免疫吸附测定(ELISA)、血凝抑制试验(HI)和病毒中和试验的结果表明,单克隆抗体11G12能够特异性识别并中和1类和0类分支的H5型血凝素,与H5N1病毒的任何其他分支均无交叉反应。在ELISA中,单克隆抗体11G12用于区分和定量三价疫苗混合物中H5N1毒株A/越南/1203/04的表达。对逃逸突变体的测序确定,单克隆抗体11G12靶向流感H5血凝素的一个主要中和表位。该研究表明,早期毒株H5中的一些主要中和表位因抗原漂移而发生了突变。