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

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ACS Nano


. 2021 Jan 22.
doi: 10.1021/acsnano.0c10180. Online ahead of print.
Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles


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

• 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.