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

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

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. Design of immunogens and strategies that can induce protective broadly neutralizing antibodies (bnAbs) is a priority for HIV vaccine development. Andrabi et al. design a chimpanzee simian immunodeficiency virus (SIV) envelope trimer immunogen that binds specifically to HIV V2-apex bnAbs and their unmutated versions. The SIV trimer immunogen induces HIV-specific neutralizing antibodies (nAbs) in a favorable animal model.

broadly neutralizing antibodies, chimpanzee SIV envelope trimer, glycan shield, HIV envelope trimer, HIV vaccine, human immunodeficiency virus, immunization strategies, simian immunodeficiency virus, V2-apex bnAb site
2211-1247
2426-2441.e6
Andrabi, Raiees
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Pallesen, Jesper
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Allen, Joel D.
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Song, Ge
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Zhang, Jinsong
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de Val, Natalia
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Gegg, Gavin
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Porter, Katelyn
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Su, Ching Yao
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Pauthner, Matthias
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Newman, Amanda
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Bouton-Verville, Hilary
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Garces, Fernando
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Wilson, Ian A.
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Crispin, Max
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Hahn, Beatrice H.
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Haynes, Barton F.
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Verkoczy, Laurent
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Ward, Andrew B.
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Burton, Dennis R.
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Andrabi, Raiees
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Pallesen, Jesper
4c823bd4-51f5-4b71-a1d4-ae9c1668ad78
Allen, Joel D.
c873d886-2a66-475b-ae04-57a10b37e716
Song, Ge
be91c0bc-98ce-40e4-af78-41547b440644
Zhang, Jinsong
3d0e1832-f212-4f69-a100-43e585643a25
de Val, Natalia
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Gegg, Gavin
0517ecd6-53b5-4393-aaf4-73870bc4dbe8
Porter, Katelyn
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Su, Ching Yao
f17d6bf1-d376-40ba-8f14-af7275daeda0
Pauthner, Matthias
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Newman, Amanda
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Bouton-Verville, Hilary
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Garces, Fernando
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Wilson, Ian A.
7865d500-d638-4a67-ad6d-fefad0ae83bb
Crispin, Max
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Hahn, Beatrice H.
759288ba-d126-422f-837f-28c5a87e63ca
Haynes, Barton F.
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Verkoczy, Laurent
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Ward, Andrew B.
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Burton, Dennis R.
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Andrabi, Raiees, Pallesen, Jesper, Allen, Joel D., Song, Ge, Zhang, Jinsong, de Val, Natalia, Gegg, Gavin, Porter, Katelyn, Su, Ching Yao, Pauthner, Matthias, Newman, Amanda, Bouton-Verville, Hilary, Garces, Fernando, Wilson, Ian A., Crispin, Max, Hahn, Beatrice H., Haynes, Barton F., Verkoczy, Laurent, Ward, Andrew B. and Burton, Dennis R. (2019) The chimpanzee SIV envelope trimer: Structure and deployment as an HIV vaccine template. Cell Reports, 27 (8), 2426-2441.e6. (doi:10.1016/j.celrep.2019.04.082).

Record type: Article

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) 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. Design of immunogens and strategies that can induce protective broadly neutralizing antibodies (bnAbs) is a priority for HIV vaccine development. Andrabi et al. design a chimpanzee simian immunodeficiency virus (SIV) envelope trimer immunogen that binds specifically to HIV V2-apex bnAbs and their unmutated versions. The SIV trimer immunogen induces HIV-specific neutralizing antibodies (nAbs) in a favorable animal model.

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Accepted/In Press date: 17 April 2019
e-pub ahead of print date: 21 May 2019
Published date: 21 May 2019
Keywords: broadly neutralizing antibodies, chimpanzee SIV envelope trimer, glycan shield, HIV envelope trimer, HIV vaccine, human immunodeficiency virus, immunization strategies, simian immunodeficiency virus, V2-apex bnAb site

Identifiers

Local EPrints ID: 431365
URI: http://eprints.soton.ac.uk/id/eprint/431365
ISSN: 2211-1247
PURE UUID: fd7dfcbc-4a60-4019-88fe-e03e9c8c3a47
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 30 May 2019 16:30
Last modified: 07 Oct 2020 02:15

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Contributors

Author: Raiees Andrabi
Author: Jesper Pallesen
Author: Joel D. Allen
Author: Ge Song
Author: Jinsong Zhang
Author: Natalia de Val
Author: Gavin Gegg
Author: Katelyn Porter
Author: Ching Yao Su
Author: Matthias Pauthner
Author: Amanda Newman
Author: Hilary Bouton-Verville
Author: Fernando Garces
Author: Ian A. Wilson
Author: Max Crispin ORCID iD
Author: Beatrice H. Hahn
Author: Barton F. Haynes
Author: Laurent Verkoczy
Author: Andrew B. Ward
Author: Dennis R. Burton

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