Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses
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; Caniels, Tom G; van der Linden, Cynthia A; Ravichandran, Rashmi; Villaudy, Julien; van der Velden, Yme U; Sliepen, Kwinten; van Gils, Marit J; Ward, Andrew B; King, Neil P; Heck, Albert J R; Sanders, Rogier W
(2022) iScience, volume 25, issue 12, pp. 1 - 22
(Article)
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
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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.
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Keywords: Immune response, Immunology, Microbiology, Virology, General
ISSN: 2589-0042
Publisher: Elsevier
Note: Funding Information: We thank P. Bieniasz for kindly sharing the pHIV-1NL43ΔENV-NanoLuc and SARS-CoV-2-SΔ19 plasmids. We thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion adjuvant. This work was supported by a Netherlands Organization for Scientific Research (NWO) Vici grant (to R.W.S.); by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923, OPP1132237, and INV-002022 (to R.W.S. and/or N.P.K.); by the Fondation Dormeur (to R.W.S. and to M.J.v.G.). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC. A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028. The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing—Original draft, Visualization, Project administration, M.B.; Conceptualization, Methodology, Investigation, Writing—Original draft, T.V.; Conceptualization, Methodology, Validation, Investigation, Project administration, P.J.M.B.; Investigation, Writing—Original draft, H.T.; Investigation, M.P.; J.A.B. J.H.B. I.B. C.A.v.d.L. R.R.; Conceptualization, Writing—Original draft, K.S.; Methodology, J.V.; Conceptualization, Methodology, Supervision, Project administration, Y.v.d.V.; Conceptualization, Methodology, Supervision, Project administration, Funding acquisition, M.J.v.G.; Resources, Supervision, Writing—Review and editing, A.B.W. N.P.K. A.J.R.H.; Conceptualization, Validation, Resources, Writing—Review and editing, Supervision, Project administration, Funding acquisition, R.W.S. N.P.K. is a cofounder, shareholder, and chair of the scientific advisory board of Icosavax, Inc. Amsterdam UMC has filed a patent application concerning the SARS-CoV-2 mAbs described in Brouwer et al.7 N.P.K. has a non-provisional US patent, no. 14/930,792, related to I53-50.53 All other authors declare no competing interests. Funding Information: We thank P. Bieniasz for kindly sharing the pHIV-1 NL43 ΔENV-NanoLuc and SARS-CoV-2-S Δ19 plasmids. We thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion adjuvant. This work was supported by a Netherlands Organization for Scientific Research ( NWO ) Vici grant (to R.W.S.); by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923 , OPP1132237 , and INV-002022 (to R.W.S. and/or N.P.K.); by the Fondation Dormeur (to R.W.S. and to M.J.v.G.). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC. A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028 . The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Publisher Copyright: © 2022 The Author(s)
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