9NHJ

AMC016 v4.2 in complex with FP-A pAb from animal RQk18 at week 43

This is a non-PDB format compatible entry.

Summary for 9NHJ

• Entry DOI: 10.2210/pdb9nhj/pdb
• EMDB information: 49413
• Descriptor: RQk-FP-A pAb heavy chain, RQk-FP-A pAb light chain, AMC016 v4.2 envelope glycoprotein gp120, ... (8 entities in total)
• Functional Keywords: hiv-1, polyclonal, cryoempem, structural protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 8
• Total formula weight: 263704.55

Authors

Pratap, P.P.,Ozorowski, G.,Ward, A.B. (deposition date: 2025-02-24, release date: 2025-06-25)

Primary citation

Pratap, P.P.,Cottrell, C.A.,Quinn, J.,Carnathan, D.G.,Bader, D.L.V.,Tran, A.S.,Enemuo, C.A.,Ngo, J.T.,Richey, S.T.,Gao, H.,Shen, X.,Greene, K.M.,Hurtado, J.,Michaels, K.K.,Ben-Akiva, E.,Allen, J.D.,Ozorowski, G.,Crispin, M.,Briney, B.,Montefiori, D.,Silvestri, G.,Irvine, D.J.,Crotty, S.,Ward, A.B.
Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.
Biorxiv, 2024

PubMed Abstract: During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.

PubMed: 39651156
DOI: 10.1101/2024.11.27.625755

Experimental method

ELECTRON MICROSCOPY (3.04 Å)