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Structure paper

タイトル	Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.
ジャーナル・号・ページ	Nature, Vol. 570, Issue 7762, Page 468-473, Year 2019
掲載日	2019年5月29日
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 /
PubMed 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.
リンク	Nature / PubMed:31142836 / PubMed Central
手法	EM (単粒子)
解像度	3.9 - 4.4 Å
構造データ	20175 6orn EMDB-20175, PDB-6orn: Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch bNAb 10-1074 手法: EM (単粒子) / 解像度: 4.05 Å 20176 6oro EMDB-20176, PDB-6oro: Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab874NHP 手法: EM (単粒子) / 解像度: 3.9 Å 20177 6orp EMDB-20177, PDB-6orp: Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab897NHP 手法: EM (単粒子) / 解像度: 4.4 Å 20178 6orq EMDB-20178, PDB-6orq: Modified BG505 SOSIP-based immunogen RC1 in complex with the elicited V3-glycan patch antibody Ab275MUR 手法: EM (単粒子) / 解像度: 4.4 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン
由来	human immunodeficiency virus 1 (ヒト免疫不全ウイルス) homo sapiens (ヒト) macaca mulatta (アカゲザル) Mus musculoides (ネズミ) mus musculus (ハツカネズミ)
キーワード	VIRAL PROTEIN/Immune System (ウイルス性) / HIV-1 broadly-neutralizing antibody / Env trimer structure / V3-glycan patch / cryo-EM (低温電子顕微鏡法) / RC1 / immunogen design / ANTIVIRAL PROTEIN-IMMUNE SYSTEM complex (抗ウイルス薬) / ANTIVIRAL PROTEIN / VIRAL PROTEIN-Immune System complex (ウイルス性)