7BPK

Zika virus envelope protein mutant bound to mAb

Summary for 7BPK

• Entry DOI: 10.2210/pdb7bpk/pdb
• Descriptor: Envelope protein, Z3L1 Heavy chain, IG c307_light_IGLV1-51_IGLJ2 (3 entities in total)
• Functional Keywords: zika virus, envelop protein, monoclonal antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Zika virus (ZIKV); More
• Total number of polymer chains: 6
• Total formula weight: 141987.37

Authors

Dai, L.,Qi, J.,Gao, G.F. (deposition date: 2020-03-23, release date: 2021-03-24, Last modification date: 2024-11-20)

Primary citation

Dai, L.,Xu, K.,Li, J.,Huang, Q.,Song, J.,Han, Y.,Zheng, T.,Gao, P.,Lu, X.,Yang, H.,Liu, K.,Xia, Q.,Wang, Q.,Chai, Y.,Qi, J.,Yan, J.,Gao, G.F.
Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch.
Nat.Immunol., 22:958-968, 2021

PubMed Abstract: Antibody-dependent enhancement (ADE) is an important safety concern for vaccine development against dengue virus (DENV) and its antigenically related Zika virus (ZIKV) because vaccine may prime deleterious antibodies to enhance natural infections. Cross-reactive antibodies targeting the conserved fusion loop epitope (FLE) are known as the main sources of ADE. We design ZIKV immunogens engineered to change the FLE conformation but preserve neutralizing epitopes. Single vaccination conferred sterilizing immunity against ZIKV without ADE of DENV-serotype 1-4 infections and abrogated maternal-neonatal transmission in mice. Unlike the wild-type-based vaccine inducing predominately cross-reactive ADE-prone antibodies, B cell profiling revealed that the engineered vaccines switched immunodominance to dispersed patterns without DENV enhancement. The crystal structure of the engineered immunogen showed the dimeric conformation of the envelope protein with FLE disruption. We provide vaccine candidates that will prevent both ZIKV infection and infection-/vaccination-induced DENV ADE.

PubMed: 34267374
DOI: 10.1038/s41590-021-00966-6

Experimental method

X-RAY DIFFRACTION (3.1 Å)