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

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

doi:10.1038/s41467-019-12080-1

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

Nat Commun. 2019 Sep 19;10(1):4272. doi: 10.1038/s41467-019-12080-1.

Authors

Philip J M Brouwer¹, Aleksandar Antanasijevic², Zachary Berndsen², Anila Yasmeen³, Brooke Fiala^{4

5}, Tom P L Bijl¹, Ilja Bontjer¹, Jacob B Bale^{4

5

6}, William Sheffler^{4

5}, Joel D Allen⁷, Anna Schorcht¹, Judith A Burger¹, Miguel Camacho¹, Daniel Ellis^{4

5}, Christopher A Cottrell², Anna-Janina Behrens^{8

9}, Marco Catalano¹, Iván Del Moral-Sánchez¹, Thomas J Ketas³, Celia LaBranche¹⁰, Marit J van Gils¹, Kwinten Sliepen¹, Lance J Stewart^{4

5}, Max Crispin^{7

8}, David C Montefiori¹⁰, David Baker^{4

5

11}, John P Moore³, Per Johan Klasse³, Andrew B Ward², Neil P King^{12

13}, Rogier W Sanders¹⁴

Affiliations

¹ Amsterdam UMC, Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands.
² Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.
³ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, 10065, USA.
⁴ Department of Biochemistry, University of Washington, Seattle, Washington, 98195, USA.
⁵ Institute for Protein Design, University of Washington, Seattle, Washington, 98195, USA.
⁶ Arzeda Corporation, Seattle, Washington, 98119, USA.
⁷ Biological Sciences and Institute of Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK.
⁸ Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, OX1 3QU, Oxford, UK.
⁹ New England Biolabs, Inc., Ipswich, Massachussetts, 01938, USA.
¹⁰ Department of Surgery, Duke University Medical Center, Durham, North Carolina, 27710, USA.
¹¹ Howard Hughes Medical Institute, University of Washington, Seattle, Washington, 98105, USA.
¹² Department of Biochemistry, University of Washington, Seattle, Washington, 98195, USA. neilking@uw.edu.
¹³ Institute for Protein Design, University of Washington, Seattle, Washington, 98195, USA. neilking@uw.edu.
¹⁴ Amsterdam UMC, Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, 1105AZ, The Netherlands. r.w.sanders@amc.uva.nl.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines / immunology
Animals
Antibodies, Neutralizing / immunology*
Antigens, Viral / biosynthesis
Antigens, Viral / immunology*
Cell Line
Epitopes / immunology
HEK293 Cells
HIV Antibodies / immunology*
HIV-1 / immunology*
Humans
Molecular Docking Simulation
Nanoparticles
Protein Multimerization / immunology
Protein Structure, Tertiary
Rabbits
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

AIDS Vaccines
Antibodies, Neutralizing
Antigens, Viral
Epitopes
HIV Antibodies
env Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding