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-Structure paper
タイトル | Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations. |
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ジャーナル・号・ページ | Nat Commun, Vol. 8, Issue 1, Page 1732, Year 2017 |
掲載日 | 2017年11月23日 |
![]() | Wilton B Williams / Jinsong Zhang / Chuancang Jiang / Nathan I Nicely / Daniela Fera / Kan Luo / M Anthony Moody / Hua-Xin Liao / S Munir Alam / Thomas B Kepler / Akshaya Ramesh / Kevin Wiehe / James A Holland / Todd Bradley / Nathan Vandergrift / Kevin O Saunders / Robert Parks / Andrew Foulger / Shi-Mao Xia / Mattia Bonsignori / David C Montefiori / Mark Louder / Amanda Eaton / Sampa Santra / Richard Scearce / Laura Sutherland / Amanda Newman / Hilary Bouton-Verville / Cindy Bowman / Howard Bomze / Feng Gao / Dawn J Marshall / John F Whitesides / Xiaoyan Nie / Garnett Kelsoe / Steven G Reed / Christopher B Fox / Kim Clary / Marguerite Koutsoukos / David Franco / John R Mascola / Stephen C Harrison / Barton F Haynes / Laurent Verkoczy / ![]() ![]() ![]() |
PubMed 要旨 | A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report ...A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice EnvB cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 1.75 - 28.1 Å |
構造データ | ![]() EMDB-9401: ![]() PDB-5ukn: ![]() PDB-5uko: ![]() PDB-5ukp: ![]() PDB-5ukq: ![]() PDB-5ukr: |
化合物 | ![]() ChemComp-CL: ![]() ChemComp-HOH: ![]() ChemComp-GOL: ![]() ChemComp-NAG: |
由来 |
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![]() | IMMUNE SYSTEM / HIV gp120 / HIV gp120 immune system |