9PM6
Cryo-EM structure of modified Zika virus E protein dimer complexed with a neutralizing antibody OZ-D4 Fab
This is a non-PDB format compatible entry.
Summary for 9PM6
| Entry DOI | 10.2210/pdb9pm6/pdb |
| EMDB information | 71728 |
| Descriptor | Envelope protein E, OZ-D4 Heavy chain, OZ-D4 Light chain (3 entities in total) |
| Functional Keywords | neutralizing antibody, viral protein, viral protein-immune system complex |
| Biological source | Zika virus More |
| Total number of polymer chains | 6 |
| Total formula weight | 188366.51 |
| Authors | |
| Primary citation | Wang, Y.,Galkin, A.,Shang, X.,Marin, A.,Jin, S.,Ye, T.J.,Bale, S.,Chiang, C.I.,Chowdhury, A.,Chenine, A.L.,Turonis, A.,Greenhouse, J.,Stone, R.,Wear, J.,Kar, S.,Andersen, H.,Huang, Y.S.,Vanlandingham, D.L.,Higgs, S.,Lapidus, R.G.,Fuerst, T.,Weber, D.J.,Wyatt, R.T.,Iffland, C.,Pierson, T.C.,Andrianov, A.K.,Pozharski, E.,Li, Y. Rational design of flavivirus E protein vaccine optimizes immunogenicity and mitigates antibody dependent enhancement risk. Nat Commun, 16:11558-11558, 2025 Cited by PubMed Abstract: Flaviviruses are a family of related viruses that cause substantial global morbidity and mortality. Vaccination against one flavivirus can sometimes exacerbate disease caused by related viruses through antibody-dependent enhancement (ADE) or interfere with the efficacy of subsequent vaccines. To address this challenge, we develop a vaccine strategy by introducing G5C/G102C mutations into the flavivirus envelope (E) glycoprotein. These mutations promote E dimerization through the formation of an inter-chain disulfide bond that conceals the immunodominant and ADE-prone fusion loop epitope (FLE). We validate this design on E proteins from multiple flaviviruses through biochemical, antigenic, and structural analyses. The resulting vaccine candidate, CC_FLE sE, derived from the Zika virus (ZIKV) and formulated with an advanced supramolecular adjuvant, provides significant protection in female mice challenged with ZIKV and prevents ADE caused by a related flavivirus, Dengue virus. In genetically modified mice expressing diverse human immunoglobulin loci, ZIKV CC_FLE sE induces robust neutralizing antibody responses targeting key ZIKV E protein epitopes, including the E-dimer-dependent epitope (EDE), indicating that ZIKV CC_FLE sE can elicit protective antibody responses within the human naïve B cell repertoire. Therefore, CC_FLE sE represents a promising strategy for developing flavivirus vaccines that minimize ADE risk while maintaining high protective efficacy. PubMed: 41429771DOI: 10.1038/s41467-025-67447-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.45 Å) |
Structure validation
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