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-Structure paper
タイトル | The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template. |
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ジャーナル・号・ページ | Cell Rep, Vol. 27, Issue 8, Page 2426-22441.e6, Year 2019 |
掲載日 | 2019年5月21日 |
著者 | Raiees Andrabi / Jesper Pallesen / Joel D Allen / Ge Song / Jinsong Zhang / Natalia de Val / Gavin Gegg / Katelyn Porter / Ching-Yao Su / Matthias Pauthner / Amanda Newman / Hilary Bouton-Verville / Fernando Garces / Ian A Wilson / Max Crispin / Beatrice H Hahn / Barton F Haynes / Laurent Verkoczy / Andrew B Ward / Dennis R Burton / |
PubMed 要旨 | Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) ...Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs. |
リンク | Cell Rep / PubMed:31116986 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.1 Å |
構造データ | EMDB-20074, PDB-6ohy: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / HIV / Cimpanzee / SIV / Env / Envelope / gp120 / gp41 / trimer / glycoprotein / simian / immunodeficiency / virus / vaccine. |