8EEZ

Crystal structure of a NHP anti-ZIKV neutralizing antibody rhMZ100-C

8EEZ の概要

• エントリーDOI: 10.2210/pdb8eez/pdb
• 分子名称: rhMZ100-C antibody heavy chain, rhMZ100-C antibody light chain (3 entities in total)
• 機能のキーワード: zikv, zikv-specific, cross-protomer epitopes, viral protein, immune system
• 由来する生物種: Macaca mulatta (Rhesus monkey); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46731.83

構造登録者

Sankhala, R.S.,Joyce, M.G. (登録日: 2022-09-07, 公開日: 2023-08-30, 最終更新日: 2024-10-30)

主引用文献

Sankhala, R.S.,Dussupt, V.,Donofrio, G.,Gromowski, G.D.,De La Barrera, R.A.,Larocca, R.A.,Mendez-Rivera, L.,Lee, A.,Choe, M.,Zaky, W.,Mantus, G.,Jensen, J.L.,Chen, W.H.,Gohain, N.,Bai, H.,McCracken, M.K.,Mason, R.D.,Leggat, D.,Slike, B.M.,Tran, U.,Jian, N.,Abbink, P.,Peterson, R.,Mendes, E.A.,Freitas de Oliveira Franca, R.,Calvet, G.A.,Bispo de Filippis, A.M.,McDermott, A.,Roederer, M.,Hernandez, M.,Albertus, A.,Davidson, E.,Doranz, B.J.,Rolland, M.,Robb, M.L.,Lynch, R.M.,Barouch, D.H.,Jarman, R.G.,Thomas, S.J.,Modjarrad, K.,Michael, N.L.,Krebs, S.J.,Joyce, M.G.
Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.
Cell Rep, 42:112942-112942, 2023

PubMed Abstract: Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

PubMed: 37561630
DOI: 10.1016/j.celrep.2023.112942

実験手法

X-RAY DIFFRACTION (2.25 Å)