8EEE

Crystal structure of a NHP anti-ZIKV neutralizing antibody rhMZ104-d in complex with ZIKV E glycoprotein

Summary for 8EEE

• Entry DOI: 10.2210/pdb8eee/pdb
• Descriptor: Envelope protein E, rhMZ104-D antibody light chain, rhMZ104-D antibody heavy chain, ... (4 entities in total)
• Functional Keywords: zikv, zikv-specific, cross-protomer epitopes, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013; More
• Total number of polymer chains: 6
• Total formula weight: 184648.99

Authors

Sankhala, R.S.,Joyce, M.G. (deposition date: 2022-09-07, release date: 2023-08-30, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.819 Å)