8G8C

Crystal structure of DH1322.1 Fab in complex with HIV proximal MPER peptide

8G8C の概要

• エントリーDOI: 10.2210/pdb8g8c/pdb
• 関連するPDBエントリー: 8G8A 8G8D
• 分子名称: DH1322.1 heavy chain, DH1322.1 light chain, Env polyprotein, ... (6 entities in total)
• 機能のキーワード: hiv, neutralizing antibody, mper, gp41, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 103304.89

構造登録者

Niyongabo, A.,Janus, B.M.,Ofek, G. (登録日: 2023-02-17, 公開日: 2024-05-22, 最終更新日: 2024-10-30)

主引用文献

Williams, W.B.,Alam, S.M.,Ofek, G.,Erdmann, N.,Montefiori, D.C.,Seaman, M.S.,Wagh, K.,Korber, B.,Edwards, R.J.,Mansouri, K.,Eaton, A.,Cain, D.W.,Martin, M.,Hwang, J.,Arus-Altuz, A.,Lu, X.,Cai, F.,Jamieson, N.,Parks, R.,Barr, M.,Foulger, A.,Anasti, K.,Patel, P.,Sammour, S.,Parsons, R.J.,Huang, X.,Lindenberger, J.,Fetics, S.,Janowska, K.,Niyongabo, A.,Janus, B.M.,Astavans, A.,Fox, C.B.,Mohanty, I.,Evangelous, T.,Chen, Y.,Berry, M.,Kirshner, H.,Van Itallie, E.,Saunders, K.O.,Wiehe, K.,Cohen, K.W.,McElrath, M.J.,Corey, L.,Acharya, P.,Walsh, S.R.,Baden, L.R.,Haynes, B.F.
Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.
Cell, 187:2919-2934.e20, 2024

PubMed Abstract: A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.

PubMed: 38761800
DOI: 10.1016/j.cell.2024.04.033

実験手法

X-RAY DIFFRACTION (2.08 Å)