ジャーナル: Nat Med / 年: 2017 タイトル: A chikungunya fever vaccine utilizing an insect-specific virus platform. 著者: Jesse H Erasmus / Albert J Auguste / Jason T Kaelber / Huanle Luo / Shannan L Rossi / Karla Fenton / Grace Leal / Dal Y Kim / Wah Chiu / Tian Wang / Ilya Frolov / Farooq Nasar / Scott C Weaver / 要旨: Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to ...Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins. The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery. Yet the recombinant virus remained completely defective for productive replication, providing a high degree of safety. A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models. In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically monitored fever. Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology.
凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV / 手法: Blot for 2 seconds before plunging
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電子顕微鏡法
顕微鏡
JEOL 3200FSC
温度
平均: 94.9 K
特殊光学系
エネルギーフィルター - 名称: Omega filter エネルギーフィルター - エネルギー下限: 0.0 eV エネルギーフィルター - エネルギー上限: 25.0 eV
日付
2014年10月17日
撮影
カテゴリ: CCD フィルム・検出器のモデル: DIRECT ELECTRON DE-20 (5k x 3k) 実像数: 348 / 平均電子線量: 60 e/Å2 詳細: 2s exposure at 16 frames per second. Movie corrected for motion and specimen damage with DE_process_frames.py written by Ben Bammes of Direct Electron, L.P.
Refined in independent halves starting from an initial model derived from low-resolution imaging on a JEM2010F
CTF補正
詳細: Each particle
最終 再構成
想定した対称性 - 点群: I (正20面体型対称) / アルゴリズム: OTHER / 解像度のタイプ: BY AUTHOR / 解像度: 9.85 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: MPSA, EMAN2 詳細: Boxing and CTF correction using EMAN2. Alignment and reconstruction using MPSA. Post-processing using EMAN2. 使用した粒子像数: 13455