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| Title | Structural and functional mapping of protective human monoclonal antibodies against enterovirus A71. |
|---|---|
| Journal, issue, pages | Sci Adv, Vol. 12, Issue 23, Page eaee8217, Year 2026 |
| Publish date | Jun 5, 2026 |
Authors | Daming Zhou / Abhay Kotecha / James T Kelly / Peng-Nien Huang / Yi-Yin Chen / Thomas S Walter / Helen M E Duyvesteyn / Raymond J Owens / Shu-Yuan Ho / Tzou-Yien Lin / Elizabeth E Fry / Jingshan Ren / Kuan-Ying A Huang / David I Stuart / ![]() |
| PubMed 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 ...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. |
External links | Sci Adv / PubMed:42247493 / PubMed Central |
| Methods | EM (single particle) / X-ray diffraction |
| Resolution | 1.14 - 4.8 Å |
| Structure data | EMDB-53994, PDB-9rig: EMDB-53995, PDB-9rih: EMDB-53996, PDB-9rii: EMDB-53997, PDB-9rij: EMDB-53998, PDB-9rik: EMDB-53999, PDB-9ril: EMDB-54000, PDB-9rim: EMDB-54001, PDB-9rin: EMDB-54002, PDB-9rio: EMDB-54003, PDB-9rip: EMDB-54004, PDB-9riq: EMDB-54005, PDB-9rir: EMDB-55620, PDB-9t6z: ![]() PDB-9i3w: ![]() PDB-9i3z: ![]() PDB-9i40: ![]() PDB-9i41: ![]() PDB-9i42: ![]() PDB-9i43: ![]() PDB-9i45: ![]() PDB-9i4b: ![]() PDB-9i4c: ![]() PDB-9i4d: ![]() PDB-9i4e: |
| Chemicals | ![]() ChemComp-BTB: ![]() ChemComp-EDO: ![]() ChemComp-HOH: ![]() ChemComp-SO4: ![]() ChemComp-GOL: ![]() ChemComp-CL: ![]() ChemComp-ACT: ![]() ChemComp-SPH: |
| Source |
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Keywords | ANTIVIRAL PROTEIN / EV71 / antibody / 16-2-8C / Fab / 16-2-12D / 16-3-4D / 16-3-3C / 16-2-2D / 16-2-9D / 16-3-10B / 17-2-12A / 17-1-12A / 17-2-2B / 34-1-6D / VIRUS / Hand-foot-and-mouth disease / HFMD / enterovirus 71 (EV-A71) / Human antibody / 17-1-2B / 16-2-11B |
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Enterovirus A71
homo sapiens (human)
chlorocebus aethiops (grivet monkey)
Keywords