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

doi:10.1016/j.isci.2022.105649

Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses

iScience. 2022 Dec 22;25(12):105649. doi: 10.1016/j.isci.2022.105649. Epub 2022 Nov 22.

Authors

Mitch Brinkkemper^{1

2}, Tim S Veth^{3

4}, Philip J M Brouwer^{1

2

5}, Hannah Turner⁵, Meliawati Poniman^{1

2}, Judith A Burger^{1

2}, Joey H Bouhuijs^{1

2}, Wouter Olijhoek^{1

2}, Ilja Bontjer^{1

2}, Jonne L Snitselaar^{1

2}, Tom G Caniels^{1

2}, Cynthia A van der Linden^{1

2}, Rashmi Ravichandran^{6

7}, Julien Villaudy^{8

9}, Yme U van der Velden^{1

2}, Kwinten Sliepen^{1

2}, Marit J van Gils^{1

2}, Andrew B Ward⁵, Neil P King^{6

7}, Albert J R Heck^{3

4}, Rogier W Sanders^{1

2

10}

Affiliations

¹ Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
² Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
³ 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.
⁴ Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
⁵ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁶ Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
⁷ Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
⁸ J&S Preclinical Solutions, 5345 RR, OSS, the Netherlands.
⁹ AIMM Therapeutics BV, 1105 BA Amsterdam, the Netherlands.
¹⁰ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.

Abstract

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.

Keywords: Immune response; Immunology; Microbiology; Virology.

Grants and funding

INV-002022/GATES/Bill & Melinda Gates Foundation/United States