National Institutes of Health/National Institute Of Allergy and Infectious Diseases
P01 AI100148
米国
National Institutes of Health/National Institute of General Medical Sciences
P50 GM082545-06
米国
引用
ジャーナル: Immunity / 年: 2019 タイトル: Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope. 著者: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S ...著者: Till Schoofs / Christopher O Barnes / Nina Suh-Toma / Jovana Golijanin / Philipp Schommers / Henning Gruell / Anthony P West / Franziska Bach / Yu Erica Lee / Lilian Nogueira / Ivelin S Georgiev / Robert T Bailer / Julie Czartoski / John R Mascola / Michael S Seaman / M Juliana McElrath / Nicole A Doria-Rose / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman / 要旨: Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization ...Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.
全体 : Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1...
全体
名称: Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1074 Fab.
要素
複合体: Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1074 Fab.
複合体: B41 SOSIP.664 trimer
複合体: 10-1074 Fab
複合体: SF12 Fab
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超分子 #1: Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1...
超分子
名称: Complex of B41 SOSIP.664 trimer with three SF12 Fabs and one 10-1074 Fab. タイプ: complex / ID: 1 / 親要素: 0 詳細: Fab fragment generated by recombinant expression and complexed with the B41 SOSIP.664 trimer
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 295 K / 装置: FEI VITROBOT MARK IV 詳細: 0 blot force, 3 second blot time, 3 uL sample added to freshly glow-discharged grids.