Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses
Publication date
2022-12-22
Authors
Brinkkemper, Mitch
Veth, Tim S.
Brouwer, Philip J M
Turner, Hannah
Poniman, Meliawati
Burger, Judith A
Bouhuijs, Joey H
Olijhoek, Wouter
Bontjer, Ilja
Snitselaar, Jonne L
Editors
Advisors
Supervisors
Document Type
Article
Metadata
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License
cc_by
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, General, SDG 3 - Good Health and Well-being
Citation
Brinkkemper, M, Veth, T S, Brouwer, P J M, Turner, H, Poniman, M, Burger, J A, Bouhuijs, J H, Olijhoek, W, Bontjer, I, Snitselaar, J L, Caniels, T G, van der Linden, C A, Ravichandran, R, Villaudy, J, van der Velden, Y U, Sliepen, K, van Gils, M J, Ward, A B, King, N P, Heck, A J R & Sanders, R W 2022, 'Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses', iScience, vol. 25, no. 12, 105649, pp. 1-22. https://doi.org/10.1016/j.isci.2022.105649