Cell Rep. 2019 May 21; 27(8):2426-2441.e6.

PubMed ID: 31116986

The chimpanzee SIV envelope trimer: Structure and deployment as an HIV vaccine template

Andrabi R, Pallesen J, Allen JD, Song G, Zhang J, de Val N, Gegg G, Porter K, Su CY, Pauthner M, Newman A, Bouton-Verville H, Garces F, Wilson IA, Crispin M, Hahn BH, Haynes BF, Verkoczy L, Ward AB, Burton DR

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.