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Design of SARS-CoV-2 RBD mRNA Vaccine Using Novel Ionizable Lipids

Uri Elia, Srinivas Ramishetti, Niels Dammes, Erez Bar-Haim, Gonna Somu Naidu, Efi Makdasi, Ofer Cohen, Dan Peer
doi: https://doi.org/10.1101/2020.10.15.341537
Uri Elia
1Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv, 69978 Israel
2Center for Nanoscience and Nanotechnology, Tel Aviv, 69978 Israel
3Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv, 69978 Israel
4Cancer Biology Research Center, Tel Aviv University, Tel Aviv, 69978 Israel
5Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100 Israel
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Srinivas Ramishetti
1Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv, 69978 Israel
2Center for Nanoscience and Nanotechnology, Tel Aviv, 69978 Israel
3Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv, 69978 Israel
4Cancer Biology Research Center, Tel Aviv University, Tel Aviv, 69978 Israel
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Niels Dammes
1Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv, 69978 Israel
2Center for Nanoscience and Nanotechnology, Tel Aviv, 69978 Israel
3Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv, 69978 Israel
4Cancer Biology Research Center, Tel Aviv University, Tel Aviv, 69978 Israel
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Erez Bar-Haim
5Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100 Israel
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Gonna Somu Naidu
1Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv, 69978 Israel
2Center for Nanoscience and Nanotechnology, Tel Aviv, 69978 Israel
3Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv, 69978 Israel
4Cancer Biology Research Center, Tel Aviv University, Tel Aviv, 69978 Israel
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Efi Makdasi
6Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 76100 Israel
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Ofer Cohen
5Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100 Israel
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  • For correspondence: peer@tauex.tau.ac.il oferc@iibr.goc.il
Dan Peer
1Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv, 69978 Israel
2Center for Nanoscience and Nanotechnology, Tel Aviv, 69978 Israel
3Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv, 69978 Israel
4Cancer Biology Research Center, Tel Aviv University, Tel Aviv, 69978 Israel
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  • For correspondence: peer@tauex.tau.ac.il oferc@iibr.goc.il
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Abstract

The novel coronavirus SARS-CoV-2 has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of various immunization approaches. mRNA vaccines represent a cell-free, simple and rapid platform for immunization, and therefore have been employed in recent studies towards the development of a SARS-CoV-2 vaccine. In this study, we present the design of a lipid nanoparticles (LNP)-encapsulated receptor binding domain (RBD) mRNA vaccine. Several ionizable lipids have been evaluated in vivo in a luciferase mRNA reporter assay, and two leading LNPs formulation have been chosen for the subsequent RBD mRNA vaccine experiment. Intramuscular administration of LNP RBD mRNA elicited robust humoral response, high level of neutralizing antibodies and a Th1-biased cellular response in BALB/c mice. These novel lipids open new avenues for mRNA vaccines in general and for a COVID19 vaccine in particular.

Competing Interest Statement

D.P. declares financial interests in ART Bioscience. None of them relates to this work. The rest of the authors declare no financial interests.

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 October 15, 2020.
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Design of SARS-CoV-2 RBD mRNA Vaccine Using Novel Ionizable Lipids
Uri Elia, Srinivas Ramishetti, Niels Dammes, Erez Bar-Haim, Gonna Somu Naidu, Efi Makdasi, Ofer Cohen, Dan Peer
bioRxiv 2020.10.15.341537; doi: https://doi.org/10.1101/2020.10.15.341537
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Design of SARS-CoV-2 RBD mRNA Vaccine Using Novel Ionizable Lipids
Uri Elia, Srinivas Ramishetti, Niels Dammes, Erez Bar-Haim, Gonna Somu Naidu, Efi Makdasi, Ofer Cohen, Dan Peer
bioRxiv 2020.10.15.341537; doi: https://doi.org/10.1101/2020.10.15.341537

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