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

Jan 22, 2021ACS nano

Design of a COVID-19 mRNA Vaccine Targeting the Virus’s Binding Site and Delivered by Fat-Based Particles

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Abstract

Intramuscular administration of LNP RBD-hFc mRNA in BALB/c mice elicited a robust humoral response and a high level of neutralizing antibodies.

Lipid nanoparticles (LNPs) were utilized to encapsulate the SARS-CoV-2 receptor-binding domain.
Two leading LNP formulations were identified through a luciferase mRNA reporter assay.
The mRNA vaccine strategy resulted in a Th1-biased cellular response.
The findings suggest that these lipids could be promising candidates for mRNA vaccines targeting COVID-19.

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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 evaluatedin 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. in vivo

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

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