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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • May 21, 2019

Published In

Volume / Issue

  • 27 / 8

Start / End Page

  • 2426 - 2441.e6

PubMed ID

  • 31116986

Pubmed Central ID

  • PMC6533203

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.04.082


  • eng

Conference Location

  • United States