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-Structure paper
| タイトル | Rational design of flavivirus E protein vaccine optimizes immunogenicity and mitigates antibody dependent enhancement risk. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 11558, Year 2025 |
| 掲載日 | 2025年12月22日 |
著者 | Yimeng Wang / Andrey Galkin / Xiaoran Shang / Alexander Marin / Shaohua Jin / Ting-Juan Ye / Shridhar Bale / Chi-I Chiang / Ananda Chowdhury / Agnes L Chenine / Ashley Turonis / Jack Greenhouse / Rebecca Stone / Jaclyn Wear / Swagata Kar / Hanne Andersen / Yan-Jang S Huang / Dana L Vanlandingham / Stephen Higgs / Rena G Lapidus / Thomas Fuerst / David J Weber / Richard T Wyatt / Christel Iffland / Theodore C Pierson / Alexander K Andrianov / Edwin Pozharski / Yuxing Li / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:41429771 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.45 - 7.96 Å |
| 構造データ | EMDB-70338, PDB-9od2: EMDB-71715, PDB-9pl9: ![]() EMDB-71727: West Nile virus E protein EMDB-71728, PDB-9pm6: |
| 由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / neutralizing antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex |
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万見文献について



著者
リンク







zika virus (ジカ熱ウイルス)
homo sapiens (ヒト)
japanese encephalitis virus (日本脳炎ウイルス)
キーワード