Structural and functional mapping of protective human monoclonal antibodies against enterovirus A71.
Journal
Science advances
Journal Volume
12
Journal Issue
23
Start Page
eaee8217
ISSN
2375-2548
Date Issued
2026-06-05
Author(s)
Zhou, Daming
Kotecha, Abhay
Kelly, James T
Huang, Peng-Nien
Chen, Yi-Yin
Walter, Thomas S
Duyvesteyn, Helen M E
Owens, Raymond J
Ho, Shu-Yuan
Lin, Tzou-Yien
Fry, Elizabeth E
Ren, Jingshan
Stuart, David I
Abstract
EV-A71 has been responsible for recent severe HFMD outbreaks. We report structures for 12 potently neutralizing human anti-EV-A71 monoclonal antibody Fabs, alone and complexed with virus. Most recognize the native antigenic state with epitopes that span interfaces, together covering 85% of the capsid surface. The majority (8 of 12) bind the canyon, while the others cluster around the icosahedral two- and threefold axes. Blocking SCARB2 receptor binding likely contributes to neutralization for all, and a subset induces empty particles. A predominant gene family (IGHV4-39) does not dictate a common binding pose. Long CDR-H3 loops are frequently key to binding, especially at the canyon, suggesting that antigenicity data based on antibodies with shorter CDR3s (e.g., murine) may be misleading. This dataset reveals neutralization mechanisms for recently circulating EV-A71 genotypes, which will inform immunotherapies. We demonstrate synergy in vitro between canyon binding and both two- and threefold binding antibodies to increase neutralization potency.
Publisher
American Association for the Advancement of Science
Type
journal article