Abstract
More than 65 million people have been confirmed infection with SARS-CoV-2 and more than 1 million have died from COVID-19 and this pandemic remains critical worldwide. Effective vaccines are one of the most important strategies to limit the pandemic. Here, we report a construction strategy of DNA vaccine candidates expressing full length wild type SARS-CoV-2 spike (S) protein, S1 or S2 region and their immunogenicity in mice. All DNA vaccine constructs of pCMVkan-S, -S1 and -S2 induced high levels of specific binding IgG that showed a balance of IgG1/IgG2a response. However, only the sera from mice vaccinated with pCMKkan-S or -S1 DNA vaccines could inhibit viral RBD and ACE2 interaction. The highest neutralizing antibody (NAb) titer was found in pCMVkan-S group, followed by -S1, while -S2 showed the lowest PRNT50 titers. The geometric mean titers (GMTs) were 2,551, 1,005 and 291 for pCMVkan-S, -S1 and -S2, respectively. pCMVkan-S construct vaccine also induced the highest magnitude and breadth of T cells response. Analysis of IFN-γ positive cells after stimulation with SARS-CoV-2 spike peptide pools were 2,991, 1,376 and 1,885 SFC/106 splenocytes for pCMVkan-S, -S1 and -S2, respectively. Our findings highlighted that full-length S antigen is more potent than the truncated spike (S1 or S2) in inducing of neutralizing antibody and robust T cell responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin-Converting Enzyme 2 / antagonists & inhibitors
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Angiotensin-Converting Enzyme 2 / metabolism
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Animals
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Antibodies, Neutralizing / blood
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COVID-19 / prevention & control
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COVID-19 / virology
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Cytokines / metabolism
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Female
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Immunity, Humoral*
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Immunoglobulin G / blood
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Interferon-gamma / metabolism
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Mice
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Mice, Inbred ICR
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Plasmids / genetics
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Plasmids / metabolism
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Protein Binding
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SARS-CoV-2 / genetics*
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Spike Glycoprotein, Coronavirus / genetics*
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Th1 Cells / cytology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
Substances
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Antibodies, Neutralizing
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Cytokines
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Immunoglobulin G
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Spike Glycoprotein, Coronavirus
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Vaccines, DNA
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spike protein, SARS-CoV-2
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Interferon-gamma
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Ace2 protein, mouse
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Angiotensin-Converting Enzyme 2
Grants and funding
This study was funded by National Vaccine Institute (NVI), grant no. 2563. 1/ 8, National Research Council of Thailand (NTCT), Emerging Infectious Diseases and Vaccines Cluster, Ratchadapisek Sompoch Endowment Fund, Chulalongkorn University and Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant no RA-MF-29/63. The authors would like to thank the Second Century Fund (C2F), Chulalongkorn University. EP was also supported by the Grants for Development of New Faculty Staff, Ratchadapiseksompote Endowment Fund, grant no DNS 63_031_30_009_2. WW is BioNet-Asia Co., Ltd consultant. The funder provided support in the form of budget for research materials but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the author contributions section.