tetano
Editor, Senior Moderator
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[SUP] 1 2 3 4 5 [/SUP], Srinivas Ramishetti[SUP] 1 2 3 4 [/SUP], Ronit Rosenfeld[SUP] 5 [/SUP], Niels Dammes[SUP] 1 2 3 4 [/SUP], Erez Bar-Haim[SUP] 5 [/SUP], Gonna Somu Naidu[SUP] 1 2 3 4 [/SUP], Efi Makdasi[SUP] 6 [/SUP], Yfat Yahalom-Ronen[SUP] 6 [/SUP], Hadas Tamir[SUP] 6 [/SUP], Nir Paran[SUP] 6 [/SUP], Ofer Cohen[SUP] 5 [/SUP], Dan Peer[SUP] 1 2 3 4 [/SUP]
Affiliations
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.
. 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[SUP] 1 2 3 4 5 [/SUP], Srinivas Ramishetti[SUP] 1 2 3 4 [/SUP], Ronit Rosenfeld[SUP] 5 [/SUP], Niels Dammes[SUP] 1 2 3 4 [/SUP], Erez Bar-Haim[SUP] 5 [/SUP], Gonna Somu Naidu[SUP] 1 2 3 4 [/SUP], Efi Makdasi[SUP] 6 [/SUP], Yfat Yahalom-Ronen[SUP] 6 [/SUP], Hadas Tamir[SUP] 6 [/SUP], Nir Paran[SUP] 6 [/SUP], Ofer Cohen[SUP] 5 [/SUP], Dan Peer[SUP] 1 2 3 4 [/SUP]
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.