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Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

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Vis graf over relationer

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.

OriginalsprogEngelsk
Artikelnummer324
TidsskriftNature Communications
Vol/bind12
Udgave nummer1
Sider (fra-til)324
DOI
StatusUdgivet - dec. 2021

Bibliografisk note

Funding Information:
The authors would like to express their deep gratitude to Nahla Chehabi, Andreas Freder-iksen, Benjamin Jacobsen, Elham Marjan Mohammad Alijazaeri, Ana Maria Guzu-nov, Tenna Gribfeldt Jensen, and Ditte Rahbæk Boilesen for their excellent technical assistance. Furthermore, we would like to thank Blanca Lopez Mendez at the Biophysics Facility—Protein Structure and Function Program from Center for Protein Research, Copenhagen, for her assistance with the DLS measurement and analysis, as well as the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen for their excellent facilities and support in acquiring TEM images. The authors would like to thank the flow cytometry and single cell core facility at Copenhagen University for their support and assistance. We would like to acknowledge the IT, Substrate, Logistics, and Security Departments at the Faculty of Health and Medical Sciences, University of Copenhagen for ensuring that this important work in the laboratory could continue during times of total lockdown. Novo Nordisk and Merck Millipore are thanked for their continuous and direct support of process development. Attana A/S, BioradChemometec, Eppendorf, Hamilton, Thermo Fisher scientific, and Wyatt are thanked for their swift and direct support of the project. The preclinical development presented in this article was funded through grants from Carlsberg Foundation (Sapere Aude grant), Gudbjørg og Ejnar Honorés Fond, Independent Research Fund Denmark (No 0214-00001B (SRP)), a private donation from Line and Mads Brandt Pedersen, and the European Union’s Horizon 2020 research and innovation program (No 101003608).

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