7ucf
From Proteopedia
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The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-A x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach. | The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-A x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach. | ||
| - | A naturally arising broad and potent CD4-binding site antibody with low somatic mutation.,Barnes CO, Schoofs T, Gnanapragasam PNP, Golijanin J, Huey-Tubman KE, Gruell H, Schommers P, Suh-Toma N, Lee YE, Cetrulo Lorenzi JC, Piechocka-Trocha A, Scheid JF, West AP Jr, Walker BD, Seaman MS, Klein F, Nussenzweig MC, Bjorkman PJ Sci Adv. 2022 Aug 12;8(32):eabp8155. doi: 10.1126/sciadv.abp8155. Epub 2022 Aug, 12. PMID:35960796<ref>PMID:35960796</ref> | + | A naturally arising broad and potent CD4-binding site antibody with low somatic mutation.,Barnes CO, Schoofs T, Gnanapragasam PNP, Golijanin J, Huey-Tubman KE, Gruell H, Schommers P, Suh-Toma N, Lee YE, Cetrulo Lorenzi JC, Piechocka-Trocha A, Scheid JF, West AP Jr, Walker BD, Seaman MS, Klein F, Nussenzweig MC, Bjorkman PJ Sci Adv. 2022 Aug 12;8(32):eabp8155. doi: 10.1126/sciadv.abp8155. Epub 2022 Aug , 12. PMID:35960796<ref>PMID:35960796</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Structure of the BG505 SOSIP.664 trimer in complex with neutralizing antibody Fab fragments 10-1074 and BG24
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