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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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.

Original languageEnglish
Pages (from-to)9627-9637
Number of pages11
JournalACS Nano
Volume15
Issue number6
DOIs
StatePublished - 22 Jun 2021

Funding

FundersFunder number
Lewis Trust

    Keywords

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

    Fingerprint

    Dive into the research topics of 'Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles'. Together they form a unique fingerprint.

    Cite this