Henry Dunand Carole J, Leon Paul E, Huang Min, Choi Angela, Chromikova Veronika, Ho Irvin Y, Tan Gene S, Cruz John, Hirsh Ariana, Zheng Nai-Ying, Mullarkey Caitlin E, Ennis Francis A, Terajima Masanori, Treanor John J, Topham David J, Subbarao Kanta, Palese Peter, Krammer Florian, Wilson Patrick C
The Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cell Host Microbe. 2016 Jun 8;19(6):800-13. doi: 10.1016/j.chom.2016.05.014.
Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines.
致病性H7N9禽流感病毒仍然是一个公共卫生问题,目前正在研发几种候选疫苗。评估接种疫苗后是否能诱导产生保护性抗体以及确定所靶向表位的多样性至关重要。在此,我们对由候选A/安徽/1/2013(H7N9)疫苗诱导产生的12种H7反应性人源抗体的结合和功能特性进行了表征。在被动转移攻击实验中,中和抗体和非中和抗体在体内均能保护小鼠。通过针对中和抗体产生逃逸突变变体来绘制H7血凝素抗原位点,确定了头部和茎部结构域上的独特表位。此外,本研究中产生的广泛交叉反应性非中和抗体通过Fc介导的效应细胞募集发挥保护作用。这些发现揭示了疫苗诱导抗体的重要特性,并为在疫苗背景下更好地理解人类对流感的单克隆抗体反应提供了依据。