Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

Kang Wang, Binyang Zheng, Li Zhang, Lunbiao Cui, Xuan Su, Qian Zhang, Zhenxi Guo, Yu Guo, Wei Zhang, Ling Zhu (), Fengcai Zhu (), Zihe Rao () and Xiangxi Wang ()
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Kang Wang: Nankai University
Binyang Zheng: Nankai University
Li Zhang: Jiangsu Provincial Center for Disease Control and Prevention
Lunbiao Cui: Jiangsu Provincial Center for Disease Control and Prevention
Xuan Su: Nankai University
Qian Zhang: Nankai University
Zhenxi Guo: Peking University
Yu Guo: Nankai University
Wei Zhang: Nankai University
Ling Zhu: Chinese Academy of Sciences
Fengcai Zhu: Jiangsu Provincial Center for Disease Control and Prevention
Zihe Rao: Nankai University
Xiangxi Wang: Nankai University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.

Date: 2020
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DOI: 10.1038/s41467-020-18250-w

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