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

Publication ,  Journal Article
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 ...
Published in: Cell Rep
May 21, 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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

May 21, 2019

Volume

27

Issue

8

Start / End Page

2426 / 2441.e6

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Recombinant Proteins
  • Protein Structure, Quaternary
  • Protein Engineering
  • Precursor Cells, B-Lymphoid
  • Pan troglodytes
  • Mutagenesis, Site-Directed
  • Models, Animal
  • Mice, Inbred C57BL
 

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Andrabi, R., Pallesen, J., Allen, J. D., Song, G., Zhang, J., de Val, N., … Burton, D. R. (2019). The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template. Cell Rep, 27(8), 2426-2441.e6. https://doi.org/10.1016/j.celrep.2019.04.082
Andrabi, Raiees, Jesper Pallesen, Joel D. Allen, Ge Song, Jinsong Zhang, Natalia de Val, Gavin Gegg, et al. “The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template.Cell Rep 27, no. 8 (May 21, 2019): 2426-2441.e6. https://doi.org/10.1016/j.celrep.2019.04.082.
Andrabi R, Pallesen J, Allen JD, Song G, Zhang J, de Val N, et al. The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template. Cell Rep. 2019 May 21;27(8):2426-2441.e6.
Andrabi, Raiees, et al. “The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template.Cell Rep, vol. 27, no. 8, May 2019, pp. 2426-2441.e6. Pubmed, doi:10.1016/j.celrep.2019.04.082.
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. The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template. Cell Rep. 2019 May 21;27(8):2426-2441.e6.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

May 21, 2019

Volume

27

Issue

8

Start / End Page

2426 / 2441.e6

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Recombinant Proteins
  • Protein Structure, Quaternary
  • Protein Engineering
  • Precursor Cells, B-Lymphoid
  • Pan troglodytes
  • Mutagenesis, Site-Directed
  • Models, Animal
  • Mice, Inbred C57BL