9NHK

BG505-CH505 Env glycoprotein in complex with NHP pAb Base-4 isolated from animal RUu18 at week 14

This is a non-PDB format compatible entry.

Summary for 9NHK

• Entry DOI: 10.2210/pdb9nhk/pdb
• Related: 9NHH 9NHI 9NHJ 9NHL 9NHM 9NHN 9NHO 9NI9
• EMDB information: 49414
• Descriptor: RUu-Base-4 pAb heavy chain, RUu-Base-4 pAb light chain, BG505-CH505 Envelope glycoprotein gp120, ... (8 entities in total)
• Functional Keywords: hiv-1, polyclonal, cryoempem, structural protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 8
• Total formula weight: 254659.19

Authors

Pratap, P.P.,Ozorowski, G.,Ward, A.B. (deposition date: 2025-02-24, release date: 2025-06-25, Last modification date: 2025-09-03)

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.,Lemnios, A.,Melo, M.B.,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.
Npj Vaccines, 10:200-200, 2025

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: 40835839
DOI: 10.1038/s41541-025-01252-4

Experimental method

ELECTRON MICROSCOPY (4.1 Å)