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Chimpanzee SIV Envelope trimer: structure and deployment as an HIV vaccine template

By Raiees Andrabi, Jesper Pallesen, Joel Allen, Ge Song, Jinsong Zhang, Natalia de Val, Gavin Gegg, Katelyn Porter, Ching-Yao Su, Matthias Pauthner, Amanda Newman, Hilary Bouton-Vervelle, Fernando Garces, Ian A. Wilson, Max Crispin, Beatrice H. Hahn, Barton F Haynes, Laurent Verkoczy, Andrew Ward, Dennis R. Burton

Posted 01 Nov 2018
bioRxiv DOI: 10.1101/459164 (published DOI: 10.1016/j.celrep.2019.04.082)

Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. Chimpanzee SIV Envelope (Env) shares a single bnAb site, the V2-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Accordingly, we generated 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 determined the structure of the MT145K trimer by cryo-EM and showed its architecture was remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knock-in mouse with chimpanzee MT145K trimer induced HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induced responses exhibiting 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.

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