Abstract

The SARS-CoV-2 pandemic is continuing to disrupt personal lives, global healthcare systems and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits and cynomolgus macaques. The vaccine-induced immunity protected macaques against a high dose challenge, resulting in strongly reduced viral infection and replication in upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic.Funding: This work was supported by a Netherlands Organization for Scientific Research (NWO) Vici grant (to R.W.S.); by the Bill & 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.), INV-008352/OPP1153692 and OPP1196345/INV-008813 (to M.C.), and grant OPP1170236 (to A.B.W.); by the Fondation Dormeur, Vaduz (to R.W.S. and to M.J.v.G.) and Health Holland PPS-allowance LSHM20040 (to M.J.v.G.); the University of Southampton Coronavirus Response Fund (to M.C.); and by the Netherlands Organisation for Health Research and Development ZONMW (to B.L.H). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC and a COVID-19 grant from the Amsterdam Institute for Infection and Immunity. R.W.S and M.J.v.G. are recipients of support from the University of Amsterdam Proof of Concept fund (contract no. 200421) as managed by Innovation Exchange Amsterdam (IXA). The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the ‘Programme Investissements d’Avenir, managed by the ANR under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT’s facilities and imaging technologies. The NHP study received financial support from REACTing, the National Research Agency (ANR; AM-CoV-Path) and the European Infrastructure TRANSVAC2 (730964). Conflict of Interest: N.P.K. is a co-founder, shareholder, and chair of the scientific advisory board of Icosavax, Inc. All other authors declare no competing interests.Ethical Approval: The protocols were approved by the institutional ethical committee “Comité d’Ethique en Expérimentation Animale du Commissariat à l’Energie Atomique et aux Energies Alternatives” (CEtEA #44) under statement number A20-011. The study was authorized by the “Research, Innovation and Education Ministry” under registration number APAFIS#24434-2020030216532863v1.

Highlights

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe and infected more than 100 million individuals since late 2019

  • SARS-CoV-2 S proteins can be displayed on twocomponent I53-50 nanoparticles The computationally designed I53-50 nanoparticle (I53-50NP) constitutes 20 trimeric (I53-50A or variants thereof) and 12 pentameric (I53-50B.4PT1) subunits that self-assemble to form monodisperse icosahedral particles with a diameter of $30 nm (Bale et al, 2016)

  • The fusion protein was purified from transfected human embryonic kidney (HEK) 293F cell supernatant using nickel-nitrilotriacetic acid (Ni-NTA) purification followed by size exclusion chromatography (SEC)

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Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe and infected more than 100 million individuals since late 2019 (https://covid19.who.int/). SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), which manifests itself as a mild respiratory illness in most infected individuals but can lead to acute respiratory distress syndrome and death in a significant percentage of cases. Recent studies suggest that SARS-CoV-2-specific neutralizing antibody (NAb) titers are an important immune correlate of protection (Addetia et al, 2020; Yu et al, 2020). This is supported by several passive immunization studies showing that administration of potent neutralizing SARS-CoV-2-specific monoclonal antibodies (mAbs) can significantly reduce lung viral loads

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