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-Structure paper
| タイトル | Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 4272, Year 2019 |
| 掲載日 | 2019年9月19日 |
著者 | Philip J M Brouwer / Aleksandar Antanasijevic / Zachary Berndsen / Anila Yasmeen / Brooke Fiala / Tom P L Bijl / Ilja Bontjer / Jacob B Bale / William Sheffler / Joel D Allen / Anna Schorcht / Judith A Burger / Miguel Camacho / Daniel Ellis / Christopher A Cottrell / Anna-Janina Behrens / Marco Catalano / Iván Del Moral-Sánchez / Thomas J Ketas / Celia LaBranche / Marit J van Gils / Kwinten Sliepen / Lance J Stewart / Max Crispin / David C Montefiori / David Baker / John P Moore / Per Johan Klasse / Andrew B Ward / Neil P King / Rogier W Sanders / ![]() |
| PubMed 要旨 | The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. ...The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform. |
リンク | Nat Commun / PubMed:31537780 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 4.5 Å |
| 構造データ | EMDB-20261: Single Particle Electron Cryo-Microscopy Reconstruction of BG505 SOSIP-I53-50NP |
| 由来 |
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キーワード | IMMUNOGEN / nanoparticle / self-assembling / HIV / SOSIP |
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