The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template.
Journal Article (Journal Article)
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.
- Andrabi, R; Pallesen, J; Allen, JD; Song, G; Zhang, J; de Val, N; Gegg, G; Porter, K; Su, C-Y; Pauthner, M; Newman, A; Bouton-Verville, H; Garces, F; Wilson, IA; Crispin, M; Hahn, BH; Haynes, BF; Verkoczy, L; Ward, AB; Burton, DR
- May 21, 2019
Volume / Issue
- 27 / 8
Start / End Page
- 2426 - 2441.e6
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States