2. Academic Validation
  3. Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles

Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles

  • ACS Nano. 2021 Jun 22;15(6):9627-9637. doi: 10.1021/acsnano.0c10180.
Uri Elia 1 2 3 4 5,  Srinivas Ramishetti 1 2 3 4,  Ronit Rosenfeld 5,  Niels Dammes 1 2 3 4,  Erez Bar-Haim 5,  Gonna Somu Naidu 1 2 3 4,  Efi Makdasi 6,  Yfat Yahalom-Ronen 6,  Hadas Tamir 6,  Nir Paran 6,  Ofer Cohen 5,  Dan Peer 1 2 3 4
Affiliations

Affiliations

  • 1 Laboratory of Precision NanoMedicine, Shmunis School for Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
  • 2 Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
  • 3 Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel.
  • 4 Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel.
  • 5 Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
  • 6 Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
PMID: 33480671 DOI: 10.1021/acsnano.0c10180
Abstract

Severe acute respiratory syndrome coronavirus 2 (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 toward the development of a SARS-CoV-2 vaccine. Herein, we present the design of an mRNA vaccine, based on lipid nanoparticles (LNPs)-encapsulated SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc). Several ionizable lipids have been evaluated in vivo in a luciferase (luc) mRNA reporter assay, and two leading LNPs formulations have been chosen for the subsequent RBD-hFc mRNA vaccine strategy. Intramuscular administration of LNP RBD-hFc mRNA elicited robust humoral response, a high level of neutralizing Antibodies and a Th1-biased cellular response in BALB/c mice. The data in the current study demonstrate the potential of these lipids as promising candidates for LNP-based mRNA vaccines in general and for a COVID19 vaccine in particular.

Keywords

COVID-19; SARS-CoV-2; ionizable lipids; lipid nanoparticles; mRNA vaccine.

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