ジャーナル: Cell Rep / 年: 2016 タイトル: Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies. 著者: Laura E McCoy / Marit J van Gils / Gabriel Ozorowski / Terrence Messmer / Bryan Briney / James E Voss / Daniel W Kulp / Matthew S Macauley / Devin Sok / Matthias Pauthner / Sergey Menis / ...著者: Laura E McCoy / Marit J van Gils / Gabriel Ozorowski / Terrence Messmer / Bryan Briney / James E Voss / Daniel W Kulp / Matthew S Macauley / Devin Sok / Matthias Pauthner / Sergey Menis / Christopher A Cottrell / Jonathan L Torres / Jessica Hsueh / William R Schief / Ian A Wilson / Andrew B Ward / Rogier W Sanders / Dennis R Burton / 要旨: A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently ...A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design.
Complex formed by overnight incubation of Fab with Env at a 6x molar excess of Fab to Env and dilution to 0.03 mg/mL prior to grid adsorption.
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電子顕微鏡法
顕微鏡
FEI TALOS ARCTICA
撮影
フィルム・検出器のモデル: FEI CETA (4k x 4k) / 平均電子線量: 25.0 e/Å2 詳細: Stage tilts of -50, -40, -30, -20, -10, and 0 degrees were performed to increase orientation sampling.