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Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence

Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence
Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.

2041-1723
Sliepen, Kwinten
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Han, Byung Woo
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Bontjer, Ilja
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Mooij, Petra
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Garces, Fernando
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Behrens, Anna-Janina
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Rantalainen, Kimmo
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Kumar, Sonu
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Sarkar, Anita
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Brouwer, Philip J.M.
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Hua, Yuanzi
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Tolazzi, Monica
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Schermer, Edith
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Torres, Jonathan L.
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Ozorowski, Gabriel
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van der Woude, Patricia
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de la Peña, Alba Torrents
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van Breemen, Mariëlle J.
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Camacho-Sánchez, Juan Miguel
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Burger, Judith A.
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Medina-Ramírez, Max
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González, Nuria
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Alcami, Jose
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LaBranche, Celia
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Scarlatti, Gabriella
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van Gils, Marit J.
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Crispin, Max
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Montefiori, David C.
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Ward, Andrew B.
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Koopman, Gerrit
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Moore, John P.
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Shattock, Robin J.
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Bogers, Willy M.
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Wilson, Ian A.
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Sanders, Rogier W.
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Sliepen, Kwinten
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Han, Byung Woo
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Bontjer, Ilja
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Mooij, Petra
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Garces, Fernando
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Behrens, Anna-Janina
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Rantalainen, Kimmo
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Kumar, Sonu
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Sarkar, Anita
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Brouwer, Philip J.M.
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Hua, Yuanzi
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Tolazzi, Monica
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Schermer, Edith
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Torres, Jonathan L.
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Ozorowski, Gabriel
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van der Woude, Patricia
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de la Peña, Alba Torrents
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van Breemen, Mariëlle J.
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Camacho-Sánchez, Juan Miguel
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Burger, Judith A.
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Medina-Ramírez, Max
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González, Nuria
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Alcami, Jose
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LaBranche, Celia
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Scarlatti, Gabriella
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van Gils, Marit J.
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Crispin, Max
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Montefiori, David C.
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Ward, Andrew B.
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Koopman, Gerrit
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Moore, John P.
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Shattock, Robin J.
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Bogers, Willy M.
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Wilson, Ian A.
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Sanders, Rogier W.
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Sliepen, Kwinten, Han, Byung Woo, Bontjer, Ilja, Mooij, Petra, Garces, Fernando, Behrens, Anna-Janina, Rantalainen, Kimmo, Kumar, Sonu, Sarkar, Anita, Brouwer, Philip J.M., Hua, Yuanzi, Tolazzi, Monica, Schermer, Edith, Torres, Jonathan L., Ozorowski, Gabriel, van der Woude, Patricia, de la Peña, Alba Torrents, van Breemen, Mariëlle J., Camacho-Sánchez, Juan Miguel, Burger, Judith A., Medina-Ramírez, Max, González, Nuria, Alcami, Jose, LaBranche, Celia, Scarlatti, Gabriella, van Gils, Marit J., Crispin, Max, Montefiori, David C., Ward, Andrew B., Koopman, Gerrit, Moore, John P., Shattock, Robin J., Bogers, Willy M., Wilson, Ian A. and Sanders, Rogier W. (2019) Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nature Communications, 10 (1), [2355]. (doi:10.1038/s41467-019-10262-5).

Record type: Article

Abstract

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.

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Accepted/In Press date: 26 April 2019
Published date: 29 May 2019
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Identifiers

Local EPrints ID: 431639
URI: http://eprints.soton.ac.uk/id/eprint/431639
DOI: doi:10.1038/s41467-019-10262-5
ISSN: 2041-1723
PURE UUID: a934f1a8-cc31-479d-bea0-96b334c8755d
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 11 Jun 2019 16:30
Last modified: 16 Mar 2024 04:30

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Contributors

Author: Kwinten Sliepen
Author: Byung Woo Han
Author: Ilja Bontjer
Author: Petra Mooij
Author: Fernando Garces
Author: Anna-Janina Behrens
Author: Kimmo Rantalainen
Author: Sonu Kumar
Author: Anita Sarkar
Author: Philip J.M. Brouwer
Author: Yuanzi Hua
Author: Monica Tolazzi
Author: Edith Schermer
Author: Jonathan L. Torres
Author: Gabriel Ozorowski
Author: Patricia van der Woude
Author: Alba Torrents de la Peña
Author: Mariëlle J. van Breemen
Author: Juan Miguel Camacho-Sánchez
Author: Judith A. Burger
Author: Max Medina-Ramírez
Author: Nuria González
Author: Jose Alcami
Author: Celia LaBranche
Author: Gabriella Scarlatti
Author: Marit J. van Gils
Author: Max Crispin ORCID iD
Author: David C. Montefiori
Author: Andrew B. Ward
Author: Gerrit Koopman
Author: John P. Moore
Author: Robin J. Shattock
Author: Willy M. Bogers
Author: Ian A. Wilson
Author: Rogier W. Sanders

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