9OOM

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

Summary for 9OOM

• Entry DOI: 10.2210/pdb9oom/pdb
• EMDB information: 70666
• Descriptor: 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)
• Functional Keywords: immune complex, neutralizing antibody, v2 apex, mouse model, viral protein
• Biological source: Mus musculus; More
• Total number of polymer chains: 12
• Total formula weight: 396861.67

Authors

Roark, R.S.,Shapiro, L.S.,Kwong, P.D. (deposition date: 2025-05-16, release date: 2025-11-12, Last modification date: 2026-02-25)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.5 Å)