9mpx | pdb_00009mpx
Crystal structure of RM014, a macaque-derived HIV V2-apex-targeting antibody from ApexGT6 immunization
Structural highlights
Publication Abstract from PubMedAn 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. HIV broadly neutralizing antibody precursors to the Apex epitope induced in nonhuman primates.,Ma KM, Sutton HJ, Pratap PP, Steichen JM, Carnathan D, Quinn J, Kalyuzhniy O, Liguori A, Agrawal S, Baboo S, Madden P, Cottrell CA, Willis JR, Lee JH, Landais E, Hu X, Ramezani-Rad P, Ozorowski G, Lewis VR, Diedrich JK, Zhou X, Altheide TK, Phelps N, Georgeson E, Alavi NB, Lu D, Eskandarzadeh S, Kubitz M, Adachi Y, Mullen TM, Silva M, Melo MB, Himansu S, Irvine DJ, Burton DR, Yates JR 3rd, Paulson JC, Sok D, Wilson IA, Silvestri G, Ward AB, Crotty S, Schief WR Sci Immunol. 2025 Aug 22;10(110):eadt6660. doi: 10.1126/sciimmunol.adt6660. Epub , 2025 Aug 22. PMID:40845127[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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