9PIV

HIV-1 bnAb 9-71 in complex with BG505 MD39 SOSIP and RM19R

Summary for 9PIV

• Entry DOI: 10.2210/pdb9piv/pdb
• EMDB information: 71678
• Descriptor: RM19R light chain Fv, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: hiv-1, sosip, human, broadly neutralizing antibody, viral protein
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 18
• Total formula weight: 398505.90

Authors

Bader, D.L.V.,Ozorowski, G.,Ward, A.B. (deposition date: 2025-07-11, release date: 2026-03-04, Last modification date: 2026-04-29)

Primary citation

Bader, D.L.V.,Flynn, C.T.,Kalyuzhniy, O.,Ozorowski, G.,Corcoran, M.M.,Burns, A.,Altman, P.,Rouzeau, R.,Sincomb, T.,Liguori, A.,Fernandez-Quintero, M.L.,Loeffler, J.R.,Torres, J.L.,Turner, H.L.,Georgeson, E.,Zhou, A.,Voic, H.,Goo, S.,Shahin, L.,Burton, I.,Wu, M.,Stanfield, R.L.,Eskandarzadeh, S.,Lu, D.,Alavi, N.,Phelps, N.,Tingle, R.,McKenney, K.,Youhanna, J.,Amirzehni, S.,Schiffner, T.,Steichen, J.M.,Burton, D.R.,Wilson, I.A.,Karlsson Hedestam, G.B.,Landais, E.,Lee, J.H.,Sok, D.,Cottrell, C.A.,Ward, A.B.,Schief, W.R.
Structural and immunogenetic signatures guide CD4-mimetic HIV vaccine development.
Cell Rep, 45:117180-117180, 2026

PubMed Abstract: HIV vaccine strategies include aims to elicit broadly neutralizing antibodies (bnAbs) targeting the CD4-binding site, that are derived from immunoglobulin heavy-chain variable genes 1-2 (V1-2) and 1-46 (V1-46). Here, we present an integrated analysis of V1-46 bnAbs, including in vitro functional studies, cryo-electron microscopy structures of two V1-46 bnAbs (1-23 and 9-71) complexed with envelope trimers, and comprehensive structural and immunogenetic analyses, to help guide vaccine design. We show that V1-46-derived bnAbs use diverse light-chain variable (V/V) genes and LCDR3 lengths commonly found in human antibody repertoires, which generate unique LCDR3 signatures that influence both the antibody paratope and approach angle. We identify three V1-46 bnAb classes, 1B2530 (V1-47), CH235 (V3-15), and 561 (V3-20), with the 561 class further subdivided into types I and II. Our findings indicate that V1-46 priming immunogens should be tailored to each bnAb class, with 561-class bnAbs presenting optimal targets for germline-targeting vaccine design.

PubMed: 41996239
DOI: 10.1016/j.celrep.2026.117180

Experimental method

ELECTRON MICROSCOPY (3.5 Å)