Two Cross-Protective Antigen Sites on Foot-and-Mouth Disease Virus Serotype O Structurally Revealed by Broadly Neutralizing Antibodies from Cattle
Kun Li, Yong He, Ge Li, Pinghua Li, Sheng Wang, Pu Sun, Huifang Bao, Yimei Cao, Xuerong Liu, Guoqiang Zhu, Yali Song, Xingwen Bai, Xueqing Ma, Yuanfang Fu, Hong Yuan, Jing Zhang, Jian Wang, Yingli Chen, Dong Li, Zhiyong Lou, Zaixin Liu, Zengjun Lu
Abstract
FMDV is the causative agent of foot-and-mouth disease (FMD), which is one of the most contagious and economically devastating diseases of domestic animals. The antigenic structure of FMDV serotype O is rather complicated, especially for those sites that can elicit a cross-protective neutralizing antibody response. Monoclonal neutralization antibodies provide both crucial defense components against FMDV infection and valuable tools for fine analysis of the antigenic structure. In this study, we found a cluster of novel VP3-focused epitopes using 13 bnAbs against FMDV serotype O from natural host cattle, which revealed two cross-protective antigen sites on VP2 and VP3. Antibody C4 targeting this novel epitope potently promoted viral particle disassembly and RNA release before infection, which may indicate a vulnerable region of FMDV. This study reveals new structural information about cross-protective antigen sites of FMDV serotype O, providing valuable and strong support for future research on broad-spectrum vaccines against FMD.