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/10 6 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.
【초록키워드】 COVID-19, neutralizing antibody, IgG, ACE2, Vaccine, pandemic, T cells, peptide, Antigen, Protein, T cell, Viral, mice, sera, T cell responses, DNA vaccines, Critical, wild type, DNA vaccine, IgG1, IFN-γ, binding, breadth, SARS-CoV-2 spike, Stimulation, Interaction, PRNT50, balance, followed by, geometric mean, Effective vaccines, geometric mean titers, GMTs, IgG2a, positive cells, splenocytes, viral RBD, candidate, geometric mean titer, full length, full-length S, limit, robust, splenocyte, lowest, highest, died, inhibit, magnitude, expressing, infection with SARS-CoV-2, positive cell, PRNT50 titers, SARS-CoV-2 spike peptide, 【제목키워드】 Th1, SARS-CoV-2 spike protein, humoral, cell-mediated immune response, elicited,