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

Cell Rep. 2019 May 21;27(8):2426-2441.e6. doi: 10.1016/j.celrep.2019.04.082.


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.

Keywords: HIV envelope trimer; HIV vaccine; V2-apex bnAb site; broadly neutralizing antibodies; chimpanzee SIV envelope trimer; glycan shield; human immunodeficiency virus; immunization strategies; simian immunodeficiency virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / chemistry*
  • AIDS Vaccines / immunology
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antigen-Antibody Reactions
  • Cryoelectron Microscopy
  • Gene Products, env / chemistry*
  • Gene Products, env / genetics
  • Gene Products, env / immunology
  • Gene Products, env / metabolism
  • Glycosylation
  • HIV Antibodies / immunology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Mutagenesis, Site-Directed
  • Pan troglodytes / virology
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism
  • Protein Engineering
  • Protein Structure, Quaternary
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Simian Immunodeficiency Virus / metabolism*


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Gene Products, env
  • HIV Antibodies
  • Recombinant Proteins