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A scalable and highly immunogenic virus-like particle-based vaccine against SARS-CoV-2
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  • Mona Mohsen,
  • Ina Balke,
  • Simon Zinkhan,
  • Villija Zeltina,
  • Xuelan Liu,
  • Xinyue Chang,
  • Pascal S. Krenger,
  • Kevin Plattner,
  • Zahra Gharailoo,
  • Anne-Cathrine S. Vogt,
  • Gilles Augusto,
  • Marianne Zwicker,
  • Salony Roongta,
  • Dominik A. Rothen,
  • Romano Josi,
  • Joana J. da Costa,
  • Jan M. Sobczak,
  • Aleksandra Nonic,
  • Lee-Anne Brand,
  • Katja Nuss,
  • Byron Martina,
  • Daniel E. Speiser,
  • Thomas Kündig,
  • Gary T. Jennings,
  • Senta M. Walton,
  • Monique Vogel,
  • Andris Zeltins,
  • Martin Bachmann
Mona Mohsen
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie

Corresponding Author:[email protected]

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Ina Balke
Latvijas Biomedicinas petijumu un studiju centrs
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Simon Zinkhan
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Villija Zeltina
Latvijas Biomedicinas petijumu un studiju centrs
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Xuelan Liu
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Xinyue Chang
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Pascal S. Krenger
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Kevin Plattner
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Zahra Gharailoo
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Anne-Cathrine S. Vogt
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Gilles Augusto
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Marianne Zwicker
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Salony Roongta
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Dominik A. Rothen
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Romano Josi
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Joana J. da Costa
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Jan M. Sobczak
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Aleksandra Nonic
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Lee-Anne Brand
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Katja Nuss
Vetsuisse-Fakultat an der Universitat Zurich
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Byron Martina
Erasmus Universiteit Rotterdam Departement Econometrie
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Daniel E. Speiser
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Thomas Kündig
UniversitatsSpital Zurich Dermatologische Klinik
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Gary T. Jennings
Citibank Switzerland AG
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Senta M. Walton
Citibank Switzerland AG
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Monique Vogel
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Andris Zeltins
Latvijas Biomedicinas petijumu un studiju centrs
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Martin Bachmann
Inselspital Bern Universitatsklinik fur Rheumatologie Immunologie und Allergologie
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Abstract

SARS-CoV-2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock-downs, wearing masks and increased hygiene, the virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or Adenoviruses, have greatly added to our ability to keep the virus at bay, again in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long-term control of SARS-CoV-2 would be inexpensive production at large scale, ability to make multiple booster injections and long-term stability at +4 oC. Here we describe such a vaccine candidate, consisting of the SARS-CoV-2 receptor binding motif grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMV TT-RBM. Using bacterial fermenter production and continuous flow centrifugation, the productivity of the production process is estimated to be >2.5 million doses per 1000 liter fermenter run and the vaccine candidate is stable for at least 14 months at 4°C. We further demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera and antibodies induced are more cross-reactive to mutant RBDs for variants of concern (VoC). Furthermore, antibody responses are neutralizing and long-lived. This, the here presented VLP-based vaccine may be a good candidate for use as conventional vaccine in the long-term.
13 Jul 2021Submitted to Allergy
13 Jul 2021Submission Checks Completed
13 Jul 2021Assigned to Editor
18 Jul 2021Reviewer(s) Assigned
28 Jul 2021Review(s) Completed, Editorial Evaluation Pending
31 Jul 2021Editorial Decision: Revise Minor
13 Aug 20211st Revision Received
13 Aug 2021Submission Checks Completed
13 Aug 2021Assigned to Editor
16 Aug 2021Reviewer(s) Assigned
18 Aug 2021Review(s) Completed, Editorial Evaluation Pending
18 Aug 2021Editorial Decision: Accept
Jan 2022Published in Allergy volume 77 issue 1 on pages 243-257. 10.1111/all.15080