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-Structure paper
タイトル | A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses. |
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ジャーナル・号・ページ | Science, Vol. 366, Issue 6470, Year 2019 |
掲載日 | 2019年12月6日 |
著者 | Jon M Steichen / Ying-Cing Lin / Colin Havenar-Daughton / Simone Pecetta / Gabriel Ozorowski / Jordan R Willis / Laura Toy / Devin Sok / Alessia Liguori / Sven Kratochvil / Jonathan L Torres / Oleksandr Kalyuzhniy / Eleonora Melzi / Daniel W Kulp / Sebastian Raemisch / Xiaozhen Hu / Steffen M Bernard / Erik Georgeson / Nicole Phelps / Yumiko Adachi / Michael Kubitz / Elise Landais / Jeffrey Umotoy / Amanda Robinson / Bryan Briney / Ian A Wilson / Dennis R Burton / Andrew B Ward / Shane Crotty / Facundo D Batista / William R Schief / |
PubMed 要旨 | Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for ...Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens. |
リンク | Science / PubMed:31672916 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.296 - 4.42 Å |
構造データ | EMDB-7875, PDB-6dfg: EMDB-7876, PDB-6dfh: EMDB-7884: BG505 MD64 N332-GT5 SOSIP trimer in complex with BG18-like precursor HMP1 fragment antigen binding and base-binding RM20A3 fragment antigen binding EMDB-7885: BG505 MD64 N332-GT5 SOSIP trimer in complex with BG18-like precursor HMP42 fragment antigen binding and base-binding RM20A3 fragment antigen binding PDB-6oc7: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / HIV Envelope / SOSIP / germline targeting / antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / trimer / precursor antibody / IMMUNE SYSTEM / Anti-HIV antibody / Fab fragment / crystallization chaperone |