9AXI

HIV 16055.v8.3 SOSIP Env in Complex with Base and N625 Epitope pAbs from Rabbit 2463

This is a non-PDB format compatible entry.

Summary for 9AXI

• Entry DOI: 10.2210/pdb9axi/pdb
• EMDB information: 43967
• Descriptor: Transmembrane protein gp41, alpha-D-mannopyranose-(1-3)-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, ... (12 entities in total)
• Functional Keywords: hiv, empem, polyclonal antibodies, rabbit, n625, base, sosip, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 10
• Total formula weight: 283670.77

Authors

Brown, S.,Antanasijevic, A.,Ward, A.B. (deposition date: 2024-03-06, release date: 2025-01-29, Last modification date: 2025-05-14)

Primary citation

Brown, S.,Antanasijevic, A.,Sewall, L.M.,Garcia, D.M.,Brouwer, P.J.M.,Sanders, R.W.,Ward, A.B.
Anti-immune complex antibodies are elicited during repeated immunization with HIV Env immunogens.
Sci Immunol, 10:eadp5218-eadp5218, 2025

PubMed Abstract: Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated. Here, we use electron microscopy-based polyclonal epitope mapping (EMPEM) to elucidate how repeated immunization with HIV Env SOSIP immunogens results in the generation of Ab2α anti-idiotypic antibodies in rabbits and rhesus macaques. We present the structures of six anti-immune complex antibodies and find that they target idiotopes composed of framework regions of antibodies bound to Env. Examination of cryo-electron microscopy density enabled prediction of sequences for an anti-immune complex antibody, the paratope of which is enriched with aromatic amino acids. This work sheds light on current vaccine development efforts for HIV, as well as for other pathogens in which repeated exposure to antigen is required.

PubMed: 39823319
DOI: 10.1126/sciimmunol.adp5218

Experimental method

ELECTRON MICROSCOPY (3.3 Å)