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A mRNA vaccine encoding for a RBD 60-mer nanoparticle elicits neutralizing antibodies and protective immunity against the SARS-CoV-2 delta variant in transgenic K18-hACE2 mice

Pascal Brandys, Xavier Montagutelli, Irena Merenkova, Güliz T. Barut, Volker Thiel, Nicholas J. Schork, Bettina Trüeb, Laurine Conquet, Aihua Deng, Aleksandar Antanasijevic, Hyun-Ku Lee, Martine Valière, Anoop Sindhu, Gita Singh, Jens Herold
doi: https://doi.org/10.1101/2022.03.21.485224
Pascal Brandys
1Phylex BioSciences, Del Mar, CA 92014, USA
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  • For correspondence: pascal@phylexbio.com
Xavier Montagutelli
2Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, 75015 Paris, France
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Irena Merenkova
1Phylex BioSciences, Del Mar, CA 92014, USA
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Güliz T. Barut
3Institute of Virology and Immunology, University of Bern, 3147 Mittelhäusern, Switzerland
4Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
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Volker Thiel
3Institute of Virology and Immunology, University of Bern, 3147 Mittelhäusern, Switzerland
4Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
5Multidisciplinary Center for Infectious Diseases, University of Bern, 3012 Bern, Switzerland
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Nicholas J. Schork
6Translational Genomics Research Institute, Phoenix, AZ 85004, USA
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Bettina Trüeb
3Institute of Virology and Immunology, University of Bern, 3147 Mittelhäusern, Switzerland
4Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
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Laurine Conquet
2Institut Pasteur, Université Paris Cité, Mouse Genetics Laboratory, 75015 Paris, France
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Aihua Deng
7BTS Research, San Diego, CA 92121, USA
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Aleksandar Antanasijevic
8The Scripps Research Institute, La Jolla, CA 92037, USA
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Hyun-Ku Lee
9Abeomics, San Diego, CA 92121, USA
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Martine Valière
1Phylex BioSciences, Del Mar, CA 92014, USA
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Anoop Sindhu
10Aldevron LLC, Fargo, ND 58104, USA
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Gita Singh
9Abeomics, San Diego, CA 92121, USA
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Jens Herold
1Phylex BioSciences, Del Mar, CA 92014, USA
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SUMMARY

Two years into the COVID-19 pandemic there is still a need for vaccines to effectively control the spread of novel SARS-CoV-2 variants and associated cases of severe disease. Here we report a messenger RNA vaccine directly encoding for a nanoparticle displaying 60 receptor binding domains (RBDs) of SARS-CoV-2 that acts as a highly effective antigen. A construct encoding the RBD of the delta variant elicits robust neutralizing antibody response with neutralizing titers an order of magnitude above currently approved mRNA vaccines. The construct also provides protective immunity against the delta variant in a widely used transgenic mouse model. We ultimately find that the proposed mRNA RBD nanoparticle-based vaccine provides a flexible platform for rapid development and will likely be of great value in combatting current and future SARS-CoV-2 variants of concern.

Competing Interest Statement

Pascal Brandys and Jens Herold are the founders and owners of Phylex BioSciences, Inc., the company that holds IP related to RBD-NP. Pascal Brandys is a named inventor on several RBD-NP vaccine patents. The other authors declare no commercial or financial conflict of interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 22, 2022.
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A mRNA vaccine encoding for a RBD 60-mer nanoparticle elicits neutralizing antibodies and protective immunity against the SARS-CoV-2 delta variant in transgenic K18-hACE2 mice
Pascal Brandys, Xavier Montagutelli, Irena Merenkova, Güliz T. Barut, Volker Thiel, Nicholas J. Schork, Bettina Trüeb, Laurine Conquet, Aihua Deng, Aleksandar Antanasijevic, Hyun-Ku Lee, Martine Valière, Anoop Sindhu, Gita Singh, Jens Herold
bioRxiv 2022.03.21.485224; doi: https://doi.org/10.1101/2022.03.21.485224
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A mRNA vaccine encoding for a RBD 60-mer nanoparticle elicits neutralizing antibodies and protective immunity against the SARS-CoV-2 delta variant in transgenic K18-hACE2 mice
Pascal Brandys, Xavier Montagutelli, Irena Merenkova, Güliz T. Barut, Volker Thiel, Nicholas J. Schork, Bettina Trüeb, Laurine Conquet, Aihua Deng, Aleksandar Antanasijevic, Hyun-Ku Lee, Martine Valière, Anoop Sindhu, Gita Singh, Jens Herold
bioRxiv 2022.03.21.485224; doi: https://doi.org/10.1101/2022.03.21.485224

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