Abstract
SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.
Keywords:
COVID-19; SARS-CoV-2; mRNA vaccine; mRNA-LNP; nucleoside-modified mRNA.
Published by Elsevier Inc.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Neutralizing / biosynthesis*
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Antibodies, Viral / biosynthesis*
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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B-Lymphocytes / virology
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Betacoronavirus / drug effects*
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Betacoronavirus / immunology
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Betacoronavirus / pathogenicity
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / virology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / virology
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COVID-19
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COVID-19 Vaccines
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Coronavirus Infections / genetics
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Coronavirus Infections / immunology
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Coronavirus Infections / pathology
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Coronavirus Infections / prevention & control*
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Disease Models, Animal
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Furin / genetics
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Furin / immunology
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Humans
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Immunity, Humoral / drug effects
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Immunization / methods
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Immunogenicity, Vaccine
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Immunologic Memory / drug effects
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred BALB C
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Nanoparticles / administration & dosage
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Nanoparticles / chemistry
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Pandemics / prevention & control*
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Pneumonia, Viral / immunology
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Pneumonia, Viral / pathology
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Pneumonia, Viral / prevention & control*
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RNA, Messenger / genetics
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RNA, Messenger / immunology*
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RNA, Viral / genetics
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RNA, Viral / immunology*
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SARS-CoV-2
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / immunology
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Vaccines, Synthetic
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Viral Vaccines / administration & dosage*
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Viral Vaccines / biosynthesis
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Viral Vaccines / genetics
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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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
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Furin