+Search query
-Structure paper
Title | The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template. |
---|---|
Journal, issue, pages | Cell Rep, Vol. 27, Issue 8, Page 2426-22441.e6, Year 2019 |
Publish date | May 21, 2019 |
Authors | Raiees Andrabi / Jesper Pallesen / Joel D Allen / Ge Song / Jinsong Zhang / Natalia de Val / Gavin Gegg / Katelyn Porter / Ching-Yao Su / Matthias Pauthner / Amanda Newman / Hilary Bouton-Verville / Fernando Garces / Ian A Wilson / Max Crispin / Beatrice H Hahn / Barton F Haynes / Laurent Verkoczy / Andrew B Ward / Dennis R Burton / |
PubMed Abstract | 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) ...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. |
External links | Cell Rep / PubMed:31116986 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.1 Å |
Structure data | EMDB-20074, PDB-6ohy: |
Chemicals | ChemComp-NAG: |
Source |
|
Keywords | VIRAL PROTEIN / HIV / Cimpanzee / SIV / Env / Envelope / gp120 / gp41 / trimer / glycoprotein / simian / immunodeficiency / virus / vaccine. |