National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01 AI100148
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P50 GM082545-06
米国
引用
ジャーナル: Nature / 年: 2019 タイトル: Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques. 著者: Amelia Escolano / Harry B Gristick / Morgan E Abernathy / Julia Merkenschlager / Rajeev Gautam / Thiago Y Oliveira / Joy Pai / Anthony P West / Christopher O Barnes / Alexander A Cohen / ...著者: Amelia Escolano / Harry B Gristick / Morgan E Abernathy / Julia Merkenschlager / Rajeev Gautam / Thiago Y Oliveira / Joy Pai / Anthony P West / Christopher O Barnes / Alexander A Cohen / Haoqing Wang / Jovana Golijanin / Daniel Yost / Jennifer R Keeffe / Zijun Wang / Peng Zhao / Kai-Hui Yao / Jens Bauer / Lilian Nogueira / Han Gao / Alisa V Voll / David C Montefiori / Michael S Seaman / Anna Gazumyan / Murillo Silva / Andrew T McGuire / Leonidas Stamatatos / Darrell J Irvine / Lance Wells / Malcolm A Martin / Pamela J Bjorkman / Michel C Nussenzweig / 要旨: Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it ...Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
全体 : Complex of RC1 variant of BG505 SOSIP.664 trimer with three Ab275...
全体
名称: Complex of RC1 variant of BG505 SOSIP.664 trimer with three Ab275MUR Fabs and three 8ANC195 Fabs
要素
複合体: Complex of RC1 variant of BG505 SOSIP.664 trimer with three Ab275MUR Fabs and three 8ANC195 Fabs
複合体: RC1 variant of BG505 SOSIP.664 trimer
タンパク質・ペプチド: RC1 variant of HIV-1 Env glycoprotein gp41
タンパク質・ペプチド: RC1 variant of HIV-1 Env glycoprotein gp120
複合体: Ab275MUR Fab
タンパク質・ペプチド: Ab275MUR antibody Fab heavy chain
タンパク質・ペプチド: Ab275MUR antibody Fab light chain
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
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超分子 #1: Complex of RC1 variant of BG505 SOSIP.664 trimer with three Ab275...
超分子
名称: Complex of RC1 variant of BG505 SOSIP.664 trimer with three Ab275MUR Fabs and three 8ANC195 Fabs タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #3-#4 詳細: Fab fragments generated by recombinant expression and complexed with the RC1 variant of BG505 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.