Abstract
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
Keywords:
COVID-19; SARS-CoV-2; lipid nanoparticle; mRNA vaccine; mouse-adapted strain; non-human primate; protection.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Neutralizing / immunology
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Binding Sites
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COVID-19 Vaccines
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Chlorocebus aethiops
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Coronavirus Infections / genetics
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Coronavirus Infections / immunology
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Coronavirus Infections / prevention & control
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Female
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HEK293 Cells
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HeLa Cells
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Humans
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Immunogenicity, Vaccine
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Injections, Intramuscular
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Macaca fascicularis
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Male
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Mice
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Mice, Inbred ICR
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Nanoparticles / chemistry
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RNA, Messenger / genetics*
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RNA, Messenger / metabolism
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RNA, Viral / genetics*
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RNA, Viral / metabolism
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Spike Glycoprotein, Coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / metabolism
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Th1 Cells / immunology
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Vaccine Potency
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology*
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Vero Cells
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Viral Vaccines / administration & dosage
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Viral Vaccines / genetics
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Viral Vaccines / immunology*
Substances
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Antibodies, Neutralizing
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COVID-19 Vaccines
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RNA, Messenger
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RNA, Viral
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Spike Glycoprotein, Coronavirus
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Vaccines, Synthetic
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Viral Vaccines
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spike protein, SARS-CoV-2