9pz3 | pdb_00009pz3
Crystal structure of HIV Apex targeting neutralizing antibody Q12BBM-069
Structural highlights
Publication Abstract from PubMedAs a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans(1). Broadly neutralizing antibodies, although rare, can be isolated from people living with HIV, revealing conserved envelope glycoprotein (Env) sites as key targets for vaccine development(2-4). One such target is the apex of the Env spike. Here we identify a vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display that resulted in the elicitation of cross-neutralizing HIV serum antibody responses in all trimer-liposome-immunized non-human primates. Critically, we isolated monoclonal antibodies from multiple macaques that cross-neutralize divergent HIV clinical isolates. High-resolution cryogenic electron microscopy structural analyses of monoclonal antibodies from four different macaques demonstrate that they target the Env trimer apex in a manner highly similar to that of the human-infection-elicited, apex-directed broadly neutralizing antibody PG9, representing a substantial advance in HIV vaccine development. Vaccination generates broadly cross-neutralizing antibodies to the HIV Env apex.,Guenaga J, Adori M, Bale S, Phulera S, Zygouras I, Schleich FA, Castro Dopico X, Agrawal S, Ota M, Wilson R, Cluff J, Dzvelaia T, Mandolesi M, Lee WH, Walsh AA, Melo MB, Verkoczy L, Irvine DJ, Corcoran M, Wilson IA, Carnathan D, Silvestri G, Ward AB, Ozorowski G, Karlsson Hedestam GB, Wyatt RT Nature. 2026 Apr 29. doi: 10.1038/s41586-026-10429-3. PMID:42056526[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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