Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2

Abstract New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine spec...

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Main Authors: Ria Lassaunière, Charlotta Polacek, Gregers J. Gram, Anders Frische, Jeanette Linnea Tingstedt, Maren Krüger, Brigitte G. Dorner, Anthony Cook, Renita Brown, Tatyana Orekov, Tammy Putmon-Taylor, Tracey-Ann Campbell, Jack Greenhouse, Laurent Pessaint, Hanne Andersen, Mark G. Lewis, Anders Fomsgaard
Format: Article
Language:English
Published: Nature Portfolio 2021-12-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-021-00419-z
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author Ria Lassaunière
Charlotta Polacek
Gregers J. Gram
Anders Frische
Jeanette Linnea Tingstedt
Maren Krüger
Brigitte G. Dorner
Anthony Cook
Renita Brown
Tatyana Orekov
Tammy Putmon-Taylor
Tracey-Ann Campbell
Jack Greenhouse
Laurent Pessaint
Hanne Andersen
Mark G. Lewis
Anders Fomsgaard
author_facet Ria Lassaunière
Charlotta Polacek
Gregers J. Gram
Anders Frische
Jeanette Linnea Tingstedt
Maren Krüger
Brigitte G. Dorner
Anthony Cook
Renita Brown
Tatyana Orekov
Tammy Putmon-Taylor
Tracey-Ann Campbell
Jack Greenhouse
Laurent Pessaint
Hanne Andersen
Mark G. Lewis
Anders Fomsgaard
author_sort Ria Lassaunière
collection DOAJ
description Abstract New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.
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spelling doaj.art-eb1cc7b9d0d241ab959968f66a8f49b52023-11-02T04:12:20ZengNature Portfolionpj Vaccines2059-01052021-12-016111310.1038/s41541-021-00419-zPreclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2Ria Lassaunière0Charlotta Polacek1Gregers J. Gram2Anders Frische3Jeanette Linnea Tingstedt4Maren Krüger5Brigitte G. Dorner6Anthony Cook7Renita Brown8Tatyana Orekov9Tammy Putmon-Taylor10Tracey-Ann Campbell11Jack Greenhouse12Laurent Pessaint13Hanne Andersen14Mark G. Lewis15Anders Fomsgaard16Department of Virus and Microbiological Special Diagnostic, Statens Serum InstitutDepartment of Virus and Microbiological Special Diagnostic, Statens Serum InstitutDepartment of Business Support and Campus, Statens Serum InstitutDepartment of Virus and Microbiological Special Diagnostic, Statens Serum InstitutDepartment of Virus and Microbiological Special Diagnostic, Statens Serum InstitutBiological Toxins (ZBS 3), Centre for Biological Threats and Special Pathogens, Robert Koch InstituteBiological Toxins (ZBS 3), Centre for Biological Threats and Special Pathogens, Robert Koch InstituteBIOQUAL Inc.BIOQUAL Inc.BIOQUAL Inc.BIOQUAL Inc.BIOQUAL Inc.BIOQUAL Inc.BIOQUAL Inc.BIOQUAL Inc.BIOQUAL Inc.Department of Virus and Microbiological Special Diagnostic, Statens Serum InstitutAbstract New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.https://doi.org/10.1038/s41541-021-00419-z
spellingShingle Ria Lassaunière
Charlotta Polacek
Gregers J. Gram
Anders Frische
Jeanette Linnea Tingstedt
Maren Krüger
Brigitte G. Dorner
Anthony Cook
Renita Brown
Tatyana Orekov
Tammy Putmon-Taylor
Tracey-Ann Campbell
Jack Greenhouse
Laurent Pessaint
Hanne Andersen
Mark G. Lewis
Anders Fomsgaard
Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
npj Vaccines
title Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
title_full Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
title_fullStr Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
title_full_unstemmed Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
title_short Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
title_sort preclinical evaluation of a candidate naked plasmid dna vaccine against sars cov 2
url https://doi.org/10.1038/s41541-021-00419-z
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