9PY5

Q10M-055 Fab in complex with HIV-1 Env Q23 NFL TD CC3+

9PY5 の概要

• エントリーDOI: 10.2210/pdb9py5/pdb
• EMDBエントリー: 72009
• 分子名称: Q23 NFL TD CC3+ gp140, Q10M-055 Fab heavy chain, Q10M-055 Fab light chain, ... (9 entities in total)
• 機能のキーワード: hiv-1, macaque, non-human primate, nhp, v2-apex, neutralizing antibody, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 283354.35

構造登録者

Phulera, S.,Ozorowski, G.,Ward, A.B. (登録日: 2025-08-06, 公開日: 2026-06-17)

主引用文献

Guenaga, J.,Adori, M.,Bale, S.,Phulera, S.,Zygouras, I.,Schleich, F.A.,Castro Dopico, X.,Agrawal, S.,Ota, M.,Wilson, R.,Cluff, J.,Dzvelaia, T.,Mandolesi, M.,Lee, W.H.,Walsh, A.A.,Melo, M.B.,Verkoczy, L.,Irvine, D.J.,Corcoran, M.,Wilson, I.A.,Carnathan, D.,Silvestri, G.,Ward, A.B.,Ozorowski, G.,Karlsson Hedestam, G.B.,Wyatt, R.T.
Vaccination generates broadly cross-neutralizing antibodies to the HIV Env apex.
Nature, 2026

PubMed Abstract: As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans. Broadly neutralizing antibodies, although rare, can be isolated from people living with HIV, revealing conserved envelope glycoprotein (Env) sites as key targets for vaccine development. One such target is the apex of the Env spike. Here we identify a vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display that resulted in the elicitation of cross-neutralizing HIV serum antibody responses in all trimer-liposome-immunized non-human primates. Critically, we isolated monoclonal antibodies from multiple macaques that cross-neutralize divergent HIV clinical isolates. High-resolution cryogenic electron microscopy structural analyses of monoclonal antibodies from four different macaques demonstrate that they target the Env trimer apex in a manner highly similar to that of the human-infection-elicited, apex-directed broadly neutralizing antibody PG9, representing a substantial advance in HIV vaccine development.

PubMed: 42056526
DOI: 10.1038/s41586-026-10429-3

実験手法

ELECTRON MICROSCOPY (3.5 Å)