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Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle

Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle
Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle

The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.

2041-1723
Brouwer, Philip J.M.
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Antanasijevic, Aleksandar
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Berndsen, Zachary
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Yasmeen, Anila
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Fiala, Brooke
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Bijl, Tom P.L.
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Bontjer, Ilja
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Bale, Jacob B.
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Sheffler, William
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Allen, Joel D.
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Schorcht, Anna
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Burger, Judith A.
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Camacho, Miguel
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Ellis, Daniel
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Cottrell, Christopher A.
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Behrens, Anna-Janina
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Catalano, Marco
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Del Moral-Sánchez, Iván
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Ketas, Thomas J.
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LaBranche, Celia
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van Gils, Marit J.
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Sliepen, Kwinten
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Stewart, Lance J.
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Crispin, Max
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Montefiori, David C.
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Baker, David
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Moore, John P.
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Klasse, Per Johan
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Ward, Andrew B.
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King, Neil P.
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Sanders, Rogier W.
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Brouwer, Philip J.M.
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Antanasijevic, Aleksandar
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Berndsen, Zachary
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Yasmeen, Anila
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Fiala, Brooke
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Bijl, Tom P.L.
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Bontjer, Ilja
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Bale, Jacob B.
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Sheffler, William
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Allen, Joel D.
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Schorcht, Anna
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Burger, Judith A.
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Camacho, Miguel
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Ellis, Daniel
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Cottrell, Christopher A.
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Behrens, Anna-Janina
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Catalano, Marco
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Del Moral-Sánchez, Iván
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Ketas, Thomas J.
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LaBranche, Celia
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van Gils, Marit J.
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Sliepen, Kwinten
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Stewart, Lance J.
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Crispin, Max
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Montefiori, David C.
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Baker, David
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Moore, John P.
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Klasse, Per Johan
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Ward, Andrew B.
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King, Neil P.
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Sanders, Rogier W.
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Brouwer, Philip J.M., Antanasijevic, Aleksandar, Berndsen, Zachary, Yasmeen, Anila, Fiala, Brooke, Bijl, Tom P.L., Bontjer, Ilja, Bale, Jacob B., Sheffler, William, Allen, Joel D., Schorcht, Anna, Burger, Judith A., Camacho, Miguel, Ellis, Daniel, Cottrell, Christopher A., Behrens, Anna-Janina, Catalano, Marco, Del Moral-Sánchez, Iván, Ketas, Thomas J., LaBranche, Celia, van Gils, Marit J., Sliepen, Kwinten, Stewart, Lance J., Crispin, Max, Montefiori, David C., Baker, David, Moore, John P., Klasse, Per Johan, Ward, Andrew B., King, Neil P. and Sanders, Rogier W. (2019) Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle. Nature Communications, 10 (1), [4272]. (doi:10.1038/s41467-019-12080-1).

Record type: Article

Abstract

The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.

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s41467-019-12080-1 - Version of Record
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Accepted/In Press date: 16 August 2019
e-pub ahead of print date: 19 September 2019

Identifiers

Local EPrints ID: 434756
URI: http://eprints.soton.ac.uk/id/eprint/434756
ISSN: 2041-1723
PURE UUID: 26b4f017-6b74-40a2-ad5f-1134802f90e7
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 08 Oct 2019 16:30
Last modified: 18 Feb 2021 17:31

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Contributors

Author: Philip J.M. Brouwer
Author: Aleksandar Antanasijevic
Author: Zachary Berndsen
Author: Anila Yasmeen
Author: Brooke Fiala
Author: Tom P.L. Bijl
Author: Ilja Bontjer
Author: Jacob B. Bale
Author: William Sheffler
Author: Joel D. Allen
Author: Anna Schorcht
Author: Judith A. Burger
Author: Miguel Camacho
Author: Daniel Ellis
Author: Christopher A. Cottrell
Author: Anna-Janina Behrens
Author: Marco Catalano
Author: Iván Del Moral-Sánchez
Author: Thomas J. Ketas
Author: Celia LaBranche
Author: Marit J. van Gils
Author: Kwinten Sliepen
Author: Lance J. Stewart
Author: Max Crispin ORCID iD
Author: David C. Montefiori
Author: David Baker
Author: John P. Moore
Author: Per Johan Klasse
Author: Andrew B. Ward
Author: Neil P. King
Author: Rogier W. Sanders

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