9B8C

RM018 Fab in complex with Apex GT 6.2 trimer and RM20A3 Fab

This is a non-PDB format compatible entry.

Summary for 9B8C

• Entry DOI: 10.2210/pdb9b8c/pdb
• EMDB information: 44342
• Descriptor: Envelope glycoprotein gp120, 2-acetamido-2-deoxy-beta-D-glucopyranose, Transmembrane protein gp41, ... (10 entities in total)
• Functional Keywords: hiv env, immune complex, macaque antibody, viral protein, v1v2 apex, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 14
• Total formula weight: 342996.14

Authors

Pratap, P.P.,Ozorowski, G.,Ward, A.B. (deposition date: 2024-03-29, release date: 2025-07-30, Last modification date: 2025-09-03)

Primary citation

Ma, K.M.,Sutton, H.J.,Pratap, P.P.,Steichen, J.M.,Carnathan, D.,Quinn, J.,Kalyuzhniy, O.,Liguori, A.,Agrawal, S.,Baboo, S.,Madden, P.,Cottrell, C.A.,Willis, J.R.,Lee, J.H.,Landais, E.,Hu, X.,Ramezani-Rad, P.,Ozorowski, G.,Lewis, V.R.,Diedrich, J.K.,Zhou, X.,Altheide, T.K.,Phelps, N.,Georgeson, E.,Alavi, N.B.,Lu, D.,Eskandarzadeh, S.,Kubitz, M.,Adachi, Y.,Mullen, T.M.,Silva, M.,Melo, M.B.,Himansu, S.,Irvine, D.J.,Burton, D.R.,Yates 3rd, J.R.,Paulson, J.C.,Sok, D.,Wilson, I.A.,Silvestri, G.,Ward, A.B.,Crotty, S.,Schief, W.R.
HIV broadly neutralizing antibody precursors to the Apex epitope induced in nonhuman primates.
Sci Immunol, 10:eadt6660-eadt6660, 2025

PubMed Abstract: An effective prophylactic HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). bnAbs to the Apex region of the HIV envelope glycoprotein (Env) are promising targets for vaccination because of their relatively low somatic hypermutation compared with other bnAbs. Most Apex bnAbs engage Env using an exceptionally long heavy-chain complementarity-determining region 3 (HCDR3) containing specific binding motifs, which reduces bnAb precursor frequency and makes priming of rare bnAb precursors a likely limiting step in the path to Apex bnAb induction. We found that adjuvanted protein or mRNA lipid nanoparticle (LNP) immunization of rhesus macaques with ApexGT6, an Env trimer engineered to bind Apex bnAb precursors, consistently induced Apex bnAb-related precursors with long HCDR3s bearing bnAb-like sequence motifs. Cryo-electron microscopy revealed that elicited Apex bnAb-related HCDR3s had structures combining elements of several prototype Apex bnAbs. These results achieve a critical HIV vaccine development milestone in outbred primates.

PubMed: 40845127
DOI: 10.1126/sciimmunol.adt6660

Experimental method

ELECTRON MICROSCOPY (3.3 Å)