Abstract:
OBJECTIVE: Enterovirus D68 (EV-D68) is an emerging respiratory pathogen associated with acute flaccid myelitis. Currently, no approved vaccines or antiviral drugs are available. Here, we report four functionally independent neutralizing antigenic sites (I to IV) by analyses of neutralizing monoclonal antibody (MAb)-resistant mutants. Site I is located in the VP1 BC loop near the fivefold axis. Site II resides in the VP2 EF loop, and site III is situated in VP1 C-terminus; both sites are located at the south rim of the canyon. Site IV is composed of residue in VP2 βB strand and residues in the VP3 BC loop and resides around the threefold axis. The developed MAbs targeting the antigenic sites can inhibit viral binding to cells. These findings advance the understanding of the recognition of EV-D68 by neutralizing antibodies and viral evolution and immune escape and also have important implications for the development of novel EV-D68 vaccines.
摘要:
目的:肠道病毒D68(EV-D68)是一种新出现的与急性弛缓性脊髓炎相关的呼吸道病原体。目前,没有批准的疫苗或抗病毒药物。这里,我们通过分析中和单克隆抗体(MAb)抗性突变体,报告了四个功能独立的中和抗原位点(I至IV)。站点I位于五倍轴附近的VP1BC环路中。站点II位于VP2EF环路中,站点III位于VP1C端;两个站点都位于峡谷的南缘。位点IV由VP2βB链中的残基和VP3BC环中的残基组成,并位于三重轴周围。开发的靶向抗原位点的MAb可抑制病毒与细胞的结合。这些发现通过中和抗体以及病毒进化和免疫逃逸促进了对EV-D68识别的理解,并且对于新型EV-D68疫苗的开发也具有重要意义。