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PLoS One ; 16(3): e0248007, 2021.
Article in English | MEDLINE | ID: covidwho-1145483

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.


Subject(s)
Immunity, Humoral , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/immunology , Vaccines, DNA/immunology , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/blood , COVID-19/prevention & control , COVID-19/virology , Cytokines/metabolism , Female , Immunoglobulin G/blood , Interferon-gamma/metabolism , Mice , Mice, Inbred ICR , Plasmids/genetics , Plasmids/metabolism , Protein Binding , Th1 Cells/cytology , Th1 Cells/metabolism , Vaccines, DNA/genetics
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