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The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template.

Cell reports | 2019

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.

Pubmed ID: 31116986 RIS Download

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI100663
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI150590
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI120810
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI131251
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI050529
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI144371

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