9MPC

Crystal structure of the HIV V2-apex-targeting antibody RM018 from macaque

Summary for 9MPC

• Entry DOI: 10.2210/pdb9mpc/pdb
• Related: 9MPB 9MPX
• Descriptor: Fab heavy chain, Fab light chain, GLYCEROL (3 entities in total)
• Functional Keywords: hiv-1, germline-targeting vaccination, apexgt6, v2-apex antibody, immune system
• Biological source: Macaca (macaque); More
• Total number of polymer chains: 2
• Total formula weight: 48637.95

Authors

Agrawal, S.,Wilson, I.A. (deposition date: 2024-12-30, 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

X-RAY DIFFRACTION (3.3 Å)