7SGT

Domain III (EDIII) of the POWV E glycoprotein

7SGT の概要

• エントリーDOI: 10.2210/pdb7sgt/pdb
• 関連するPDBエントリー: 7KYL
• NMR情報: BMRB: 30959
• 分子名称: Envelope protein E (1 entity in total)
• 機能のキーワード: powassan virus, nanoparticle immunogen, flavivirus, monoclonal antibody, viral protein
• 由来する生物種: Tick-borne powassan virus (strain lb)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11182.76

構造登録者

Harris, R.,Cahill, S.M.,Cowburn, D. (登録日: 2021-10-07, 公開日: 2022-05-18, 最終更新日: 2024-10-16)

主引用文献

Malonis, R.J.,Georgiev, G.I.,Haslwanter, D.,VanBlargan, L.A.,Fallon, G.,Vergnolle, O.,Cahill, S.M.,Harris, R.,Cowburn, D.,Chandran, K.,Diamond, M.S.,Lai, J.R.
A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice.
Plos Pathog., 18:e1010573-e1010573, 2022

PubMed Abstract: Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and C-C' loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs.

PubMed: 35679349
DOI: 10.1371/journal.ppat.1010573

実験手法

SOLUTION NMR