iScience (Dec 2022)
Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses
- Mitch Brinkkemper,
- Tim S. Veth,
- Philip J.M. Brouwer,
- Hannah Turner,
- Meliawati Poniman,
- Judith A. Burger,
- Joey H. Bouhuijs,
- Wouter Olijhoek,
- Ilja Bontjer,
- Jonne L. Snitselaar,
- Tom G. Caniels,
- Cynthia A. van der Linden,
- Rashmi Ravichandran,
- Julien Villaudy,
- Yme U. van der Velden,
- Kwinten Sliepen,
- Marit J. van Gils,
- Andrew B. Ward,
- Neil P. King,
- Albert J.R. Heck,
- Rogier W. Sanders
Affiliations
- Mitch Brinkkemper
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Tim S. Veth
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands
- Philip J.M. Brouwer
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Hannah Turner
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Meliawati Poniman
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Judith A. Burger
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Joey H. Bouhuijs
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Wouter Olijhoek
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Ilja Bontjer
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Jonne L. Snitselaar
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Tom G. Caniels
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Cynthia A. van der Linden
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Rashmi Ravichandran
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA
- Julien Villaudy
- J&S Preclinical Solutions, 5345 RR, OSS, the Netherlands; AIMM Therapeutics BV, 1105 BA Amsterdam, the Netherlands
- Yme U. van der Velden
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Kwinten Sliepen
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Marit J. van Gils
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands
- Andrew B. Ward
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Neil P. King
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA
- Albert J.R. Heck
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands
- Rogier W. Sanders
- Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 12
p. 105649
Abstract
Summary: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses continuous challenges in combating the virus. Here, we describe vaccination strategies to broaden SARS-CoV-2 and sarbecovirus immunity by combining spike proteins based on different viruses or viral strains displayed on two-component protein nanoparticles. First, we combined spike proteins based on ancestral and Beta SARS-CoV-2 strains to broaden SARS-CoV-2 immune responses. Inclusion of Beta spike improved neutralizing antibody responses against SARS-CoV-2 Beta, Gamma, and Omicron BA.1 and BA.4/5. A third vaccination with ancestral SARS-CoV-2 spike also improved cross-neutralizing antibody responses against SARS-CoV-2 variants, in particular against the Omicron sublineages. Second, we combined SARS-CoV and SARS-CoV-2 spike proteins to broaden sarbecovirus immune responses. Adding SARS-CoV spike to a SARS-CoV-2 spike vaccine improved neutralizing responses against SARS-CoV and SARS-like bat sarbecoviruses SHC014 and WIV1. These results should inform the development of broadly active SARS-CoV-2 and pan-sarbecovirus vaccines and highlight the versatility of two-component nanoparticles for displaying diverse antigens.
