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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Cyrielle Fougeroux, AdaptVac Aps
  • ,
  • Louise Goksøyr, AdaptVac Aps, Københavns Universitet
  • ,
  • Manja Idorn
  • Vladislav Soroka, Expres 2 ion Biotechnologies Aps
  • ,
  • Sebenzile K. Myeni, Leiden University
  • ,
  • Robert Dagil, Københavns Universitet, VAR2pharmaceuticals
  • ,
  • Christoph M. Janitzek, Københavns Universitet
  • ,
  • Max Søgaard, Expres 2 ion Biotechnologies Aps
  • ,
  • Kara Lee Aves, Københavns Universitet
  • ,
  • Emma W. Horsted, Københavns Universitet
  • ,
  • Sayit Mahmut Erdoğan, Københavns Universitet, Ministry of Health Turkey
  • ,
  • Tobias Gustavsson, Københavns Universitet, VAR2pharmaceuticals
  • ,
  • Jerzy Dorosz, Expres 2 ion Biotechnologies Aps
  • ,
  • Stine Clemmensen, Expres 2 ion Biotechnologies Aps
  • ,
  • Laurits Fredsgaard, Københavns Universitet
  • ,
  • Susan Thrane, AdaptVac Aps
  • ,
  • Elena E. Vidal-Calvo, VAR2pharmaceuticals
  • ,
  • Paul Khalifé, Københavns Universitet
  • ,
  • Thomas M. Hulen, Københavns Universitet
  • ,
  • Swati Choudhary, Københavns Universitet, VAR2pharmaceuticals
  • ,
  • Michael Theisen, Københavns Universitet, Statens Serum Institut
  • ,
  • Susheel K. Singh, Københavns Universitet, Statens Serum Institut
  • ,
  • Asier Garcia-Senosiain, Københavns Universitet, Statens Serum Institut
  • ,
  • Linda Van Oosten, Laboratory of Virology
  • ,
  • Gorben Pijlman, Laboratory of Virology
  • ,
  • Bettina Hierzberger, Expres 2 ion Biotechnologies Aps
  • ,
  • Tanja Domeyer, Expres 2 ion Biotechnologies Aps
  • ,
  • Blanka W. Nalewajek, Expres 2 ion Biotechnologies Aps
  • ,
  • Anette Strøbæk, Expres 2 ion Biotechnologies Aps
  • ,
  • Magdalena Skrzypczak, Expres 2 ion Biotechnologies Aps
  • ,
  • Laura F. Andersson, Expres 2 ion Biotechnologies Aps
  • ,
  • Søren Buus, Københavns Universitet
  • ,
  • Anette Stryhn Buus, Københavns Universitet
  • ,
  • Jan Pravsgaard Christensen, Københavns Universitet
  • ,
  • Tim J. Dalebout, Leiden University
  • ,
  • Kasper Iversen, Københavns Universitet
  • ,
  • Lene H. Harritshøj, Københavns Universitet
  • ,
  • Benjamin Mordmüller, University of Tübingen, Centre de Recherches Médicales de Lambaréné
  • ,
  • Henrik Ullum, Københavns Universitet
  • ,
  • Line S. Reinert
  • Willem Adriaan de Jongh, AdaptVac Aps, Expres 2 ion Biotechnologies Aps
  • ,
  • Marjolein Kikkert, Leiden University
  • ,
  • Søren R. Paludan
  • Thor G. Theander, Københavns Universitet
  • ,
  • Morten A. Nielsen, Københavns Universitet
  • ,
  • Ali Salanti, Københavns Universitet, VAR2pharmaceuticals
  • ,
  • Adam F. Sander, AdaptVac Aps, Københavns Universitet

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
Nummer1
Antal sider11
ISSN2041-1723
DOI
StatusUdgivet - jan. 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).

Funding Information:
All authors contributed to: analyzing and discussing the data and proof-reading the manuscript. C.F. and L.G.: writing of the article, CLP, antigen and vaccine design, purification and quality control of the vaccine, mouse studies (ELISA, immunization), planning and designing CLP related experiments. All authors from Aarhus University (M.I., S.R.P., and L.S.R.): designed, performed and analyzed neutralization data. All authors from Expression Biotechnologies (V.S., M.S. (Max Søgaard), J.D., S.C. (Stine Clemensen), B.H., T.D., B.W.N., A.S., M.S (Magdalena Skrzypczak)., L.F.A.): design, production, purification, and characterization of protein constructs. All authors from Leiden University (S.K.M., T.J.D., M.K.): designed, performed, and analyzed neutralization data. R.D. and E.W.H.: designing, performing, and analyzing ACE2 binding studies. C.M.J.: designing and performing electron microscopy, DLS measurements, CLP production and purification, CLP, antigen, and vaccine design. K.L.A.: performing ELISA, CLP production and purification, CLP, antigen, and vaccine design. S.M.E., T.G., S.C. (Swati Choudhary), and E.E.V.C.: Large scale development of the VLPs, QC analytical method development for the VLPs. LF: CLP production and purification, CLP, antigen, and vaccine design. ST: contributed to the design of the Tag/Catcher system and CLP design. P.K. and T.M.H.: production, purification, and quality control of monoclonal antibodies used for ELISA studies. M.T., S.K.S., and A.G.S.: antigen design, production, and purification. All authors from Wageningen (L.V.O., G.P.): antigen design, production, and purification. B.M. (Tübingen): application for funding, providing clinical expertise. S.B., A.S.B., J.P.C.: providing support and material for T cell experiments. L.H.H., H.U., K.I.: provided human serum samples, and analysis of it. W.A.J.: creating the COVID consortium, application for funding, design of experiments, supervision of the project. T.G.T., M.A.N., A.S.: application for funding, design of experiments, supervision of the project AFS: supervising the project and writing the article, application for funding, design of experiments.

Publisher Copyright:
© 2021, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Se relationer på Aarhus Universitet Citationsformater

ID: 209765010