National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01 AI100148
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P50 AI150464
United States
Bill & Melinda Gates Foundation
OPP1124068
United States
Citation
Journal: Sci Adv / Year: 2022 Title: A naturally arising broad and potent CD4-binding site antibody with low somatic mutation. Authors: Christopher O Barnes / Till Schoofs / Priyanthi N P Gnanapragasam / Jovana Golijanin / Kathryn E Huey-Tubman / Henning Gruell / Philipp Schommers / Nina Suh-Toma / Yu Erica Lee / Julio C ...Authors: Christopher O Barnes / Till Schoofs / Priyanthi N P Gnanapragasam / Jovana Golijanin / Kathryn E Huey-Tubman / Henning Gruell / Philipp Schommers / Nina Suh-Toma / Yu Erica Lee / Julio C Cetrulo Lorenzi / Alicja Piechocka-Trocha / Johannes F Scheid / Anthony P West / Bruce D Walker / Michael S Seaman / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman / Abstract: 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, ...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-Å 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.
Mass: 21897.195 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): Expi293 / Production host: Homo sapiens (human)
#2: Antibody
BG24Fabheavychain
Mass: 25354.445 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): Expi293 / Production host: Homo sapiens (human)