9OOM

Cryo-EM structure of vaccine-elicited antibody T6_P_H03 in complex with HIV Env trimer Q23-APEX-GT1

9OOM の概要

• エントリーDOI: 10.2210/pdb9oom/pdb
• EMDBエントリー: 70666
• 分子名称: T6_P_H03 heavy chain, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• 機能のキーワード: immune complex, neutralizing antibody, v2 apex, mouse model, viral protein
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 396861.67

構造登録者

Roark, R.S.,Shapiro, L.S.,Kwong, P.D. (登録日: 2025-05-16, 公開日: 2025-11-12, 最終更新日: 2026-02-25)

主引用文献

Ghosh, A.R.,Habib, R.,Mishra, N.,Roark, R.S.,Akauliya, M.,Albowaidey, A.A.,Allen, J.D.,Amereh, K.,Avillion, G.,Bottermann, M.,Liang, B.,Chaudhary, N.,Callaghan, S.,Dye, J.,Li, X.,Ellis-Pugh, J.R.,Roy Chowdhury, R.,James, N.E.,Liu, X.,Maiorino, L.,Villavicencio, P.M.,Nedellec, R.,Oberoi, P.,Sowers, K.J.,Park, Y.,Prum, T.,Rodriguez, L.,Ssozi, M.,Torres, J.L.,Walsh, A.A.,Warner, J.E.,Weldon, S.R.,Xu, L.,Wiehe, K.,Crispin, M.,Ward, A.B.,Nair, U.,Hahn, B.H.,Burton, D.R.,Shapiro, L.,Kwong, P.D.,Irvine, D.J.,Andrabi, R.,Shaw, G.M.,Batista, F.D.
Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.
Sci Immunol, 11:eadz5064-eadz5064, 2026

PubMed Abstract: Current immunization strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multiboost regimens. In rhesus macaques, simian-human immunodeficiency virus (SHIV) infection rapidly drives the development of some bnAb classes sharing structural similarities with those in humans. Here, we generated a knockin (KI) mouse model with B cells bearing the unmutated common ancestor of a V2 apex-targeted bnAb lineage, V033-a. A single immunization with a germline-targeting native-like trimer, Q23-APEX-GT1, recapitulated the ontogeny of the mature rhesus bnAb in KI mice, including rare, disfavored somatic mutations. Resulting antibodies exhibited potent neutralization against a broad panel of heterologous HIV-1 strains. Boosting with Env escape mutant trimers further improved breadth and potency, and cryo-electron microscopy analysis revealed the structural basis for heterologous neutralization breadth. Nonhuman primate and mouse models combined with structure can serve as a platform for identifying and validating immunogens that streamline HIV vaccination regimens.

PubMed: 41686913
DOI: 10.1126/sciimmunol.adz5064

実験手法

ELECTRON MICROSCOPY (3.5 Å)