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

Uri Elia, Srinivas Ramishetti, Ronit Rosenfeld, Niels Dammes, Erez Bar-Haim, Gonna Somu Naidu, Efi Makdasi, Yfat Yahalom-Ronen, Hadas Tamir, Nir Paran, Ofer Cohen, Dan Peer

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9627-9637
Number of pages11
JournalACS Nano
Issue number6
Early online dateJan 22 2021
StatePublished - Jun 22 2021


  • COVID-19
  • SARS-CoV-2
  • ionizable lipids
  • lipid nanoparticles
  • mRNA vaccine
  • Antibodies, Neutralizing
  • Humans
  • Lipids
  • Vaccines
  • Antibodies, Viral
  • RNA, Messenger/genetics
  • Nanoparticles
  • Spike Glycoprotein, Coronavirus
  • Animals
  • COVID-19 Vaccines
  • Mice
  • Mice, Inbred BALB C

ASJC Scopus subject areas

  • Engineering(all)
  • Physics and Astronomy(all)
  • Materials Science(all)


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