The University of Southampton
×
Filter your search:
University of Southampton Institutional Repository

Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization

Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization
Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization

The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).

2211-1247
1805-1817
Torrents de la Peña, Alba
5aa8f573-c651-4d0d-b816-93544ea46457
Julien, Jean Philippe
00bf0986-eadf-4cf6-9b61-6f1500d9b0a6
de Taeye, Steven W.
3ee19998-9ef7-4630-8a9b-da852b834225
Garces, Fernando
e622015b-b62e-4024-a6ac-7ffce5d3e22f
Guttman, Miklos
08afbafa-8a25-4486-8e46-2d1be5f7b120
Ozorowski, Gabriel
9d448a80-7310-4b30-ba44-ee8b18222a02
Pritchard, Laura K.
bfa1d1b4-50b6-401f-b153-8c3322b2e726
Behrens, Anna Janina
ed584c40-79cb-4de9-bb9c-bd68c71d6a68
Go, Eden P.
4c2cbf69-492e-4e40-bc4d-9c3e979d8dc8
Burger, Judith A.
a72f1372-e14b-410a-980d-526e641ed3dc
Schermer, Edith E.
00ca2bc0-f5a7-48e5-b0de-a32ba2e150d4
Sliepen, Kwinten
d2551fe9-7d04-459e-85b5-29fc4b35317a
Ketas, Thomas J.
be22ffd5-bef3-46c4-92fe-db4466a2a098
Pugach, Pavel
9756d3e5-d6e4-466c-a348-920a101a785c
Yasmeen, Anila
2c47f610-f8ab-4b85-b33e-64837c8345cc
Cottrell, Christopher A.
942bfa7b-c09e-459d-a6c2-0d64d55fa230
Torres, Jonathan L.
8e9a3e7b-a841-4748-927b-967ac8135774
Vavourakis, Charlotte D.
1775c7e5-e653-409a-823c-2f7bff68cf21
van Gils, Marit J.
f2e1e7f1-36a1-4270-8509-d17a10ddb9a6
LaBranche, Celia
5b76e539-3714-4d68-a22a-985c5bc6c151
Montefiori, David C.
e1f1e5f0-7bed-4994-81e2-7f1e0ff5663b
Desaire, Heather
4186ab6e-fe78-4c8b-a4dc-4b8a0a27bdee
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Klasse, Per Johan
23277bb2-de88-4e9c-9b54-3fb1193e9d9e
Lee, Kelly K.
8a1eccb6-2e55-4ccd-aa23-d39f471c3c62
Moore, John P.
3c26226c-c036-48db-bbd1-828a86b29697
Ward, Andrew B.
78ce5b6a-b852-4ee4-a950-f7ff7b183d83
Wilson, Ian A.
7865d500-d638-4a67-ad6d-fefad0ae83bb
Sanders, Rogier W.
d3b67c2c-c725-42e7-b972-50b30be67c74
Torrents de la Peña, Alba
5aa8f573-c651-4d0d-b816-93544ea46457
Julien, Jean Philippe
00bf0986-eadf-4cf6-9b61-6f1500d9b0a6
de Taeye, Steven W.
3ee19998-9ef7-4630-8a9b-da852b834225
Garces, Fernando
e622015b-b62e-4024-a6ac-7ffce5d3e22f
Guttman, Miklos
08afbafa-8a25-4486-8e46-2d1be5f7b120
Ozorowski, Gabriel
9d448a80-7310-4b30-ba44-ee8b18222a02
Pritchard, Laura K.
bfa1d1b4-50b6-401f-b153-8c3322b2e726
Behrens, Anna Janina
ed584c40-79cb-4de9-bb9c-bd68c71d6a68
Go, Eden P.
4c2cbf69-492e-4e40-bc4d-9c3e979d8dc8
Burger, Judith A.
a72f1372-e14b-410a-980d-526e641ed3dc
Schermer, Edith E.
00ca2bc0-f5a7-48e5-b0de-a32ba2e150d4
Sliepen, Kwinten
d2551fe9-7d04-459e-85b5-29fc4b35317a
Ketas, Thomas J.
be22ffd5-bef3-46c4-92fe-db4466a2a098
Pugach, Pavel
9756d3e5-d6e4-466c-a348-920a101a785c
Yasmeen, Anila
2c47f610-f8ab-4b85-b33e-64837c8345cc
Cottrell, Christopher A.
942bfa7b-c09e-459d-a6c2-0d64d55fa230
Torres, Jonathan L.
8e9a3e7b-a841-4748-927b-967ac8135774
Vavourakis, Charlotte D.
1775c7e5-e653-409a-823c-2f7bff68cf21
van Gils, Marit J.
f2e1e7f1-36a1-4270-8509-d17a10ddb9a6
LaBranche, Celia
5b76e539-3714-4d68-a22a-985c5bc6c151
Montefiori, David C.
e1f1e5f0-7bed-4994-81e2-7f1e0ff5663b
Desaire, Heather
4186ab6e-fe78-4c8b-a4dc-4b8a0a27bdee
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Klasse, Per Johan
23277bb2-de88-4e9c-9b54-3fb1193e9d9e
Lee, Kelly K.
8a1eccb6-2e55-4ccd-aa23-d39f471c3c62
Moore, John P.
3c26226c-c036-48db-bbd1-828a86b29697
Ward, Andrew B.
78ce5b6a-b852-4ee4-a950-f7ff7b183d83
Wilson, Ian A.
7865d500-d638-4a67-ad6d-fefad0ae83bb
Sanders, Rogier W.
d3b67c2c-c725-42e7-b972-50b30be67c74

Torrents de la Peña, Alba, Julien, Jean Philippe, de Taeye, Steven W., Garces, Fernando, Guttman, Miklos, Ozorowski, Gabriel, Pritchard, Laura K., Behrens, Anna Janina, Go, Eden P., Burger, Judith A., Schermer, Edith E., Sliepen, Kwinten, Ketas, Thomas J., Pugach, Pavel, Yasmeen, Anila, Cottrell, Christopher A., Torres, Jonathan L., Vavourakis, Charlotte D., van Gils, Marit J., LaBranche, Celia, Montefiori, David C., Desaire, Heather, Crispin, Max, Klasse, Per Johan, Lee, Kelly K., Moore, John P., Ward, Andrew B., Wilson, Ian A. and Sanders, Rogier W. (2017) Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization. Cell Reports, 20 (8), 1805-1817. (doi:10.1016/j.celrep.2017.07.077).

Record type: Article

Abstract

The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).

Text
1-s2.0-S2211124717310720-main - Version of Record
Available under License Creative Commons Attribution Non-commercial No Derivatives.
Download (2MB)

More information

Accepted/In Press date: 26 July 2017
e-pub ahead of print date: 23 August 2017
Published date: August 2017
Related URLs:

Identifiers

Local EPrints ID: 414339
URI: http://eprints.soton.ac.uk/id/eprint/414339
DOI: doi:10.1016/j.celrep.2017.07.077
ISSN: 2211-1247
PURE UUID: 9d2c1273-6310-4762-9d0c-7bfd4d5ab8e5
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 26 Sep 2017 16:30
Last modified: 16 Mar 2024 04:30

Export record

Altmetrics

Contributors

Author: Alba Torrents de la Peña
Author: Jean Philippe Julien
Author: Steven W. de Taeye
Author: Fernando Garces
Author: Miklos Guttman
Author: Gabriel Ozorowski
Author: Laura K. Pritchard
Author: Anna Janina Behrens
Author: Eden P. Go
Author: Judith A. Burger
Author: Edith E. Schermer
Author: Kwinten Sliepen
Author: Thomas J. Ketas
Author: Pavel Pugach
Author: Anila Yasmeen
Author: Christopher A. Cottrell
Author: Jonathan L. Torres
Author: Charlotte D. Vavourakis
Author: Marit J. van Gils
Author: Celia LaBranche
Author: David C. Montefiori
Author: Heather Desaire
Author: Max Crispin ORCID iD
Author: Per Johan Klasse
Author: Kelly K. Lee
Author: John P. Moore
Author: Andrew B. Ward
Author: Ian A. Wilson
Author: Rogier W. Sanders

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Library staff additional information
Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×