RESUMO
To fight against the worldwide COVID-19 pandemic, the development of an effective and safe vaccine against SARS-CoV-2 is required. As potential pandemic vaccines, DNA/RNA vaccines, viral vector vaccines and protein-based vaccines have been rapidly developed to prevent pandemic spread worldwide. In this study, we designed plasmid DNA vaccine targeting the SARS-CoV-2 Spike glycoprotein (S protein) as pandemic vaccine, and the humoral, cellular, and functional immune responses were characterized to support proceeding to initial human clinical trials. After intramuscular injection of DNA vaccine encoding S protein with alum adjuvant (three times at 2-week intervals), the humoral immunoreaction, as assessed by anti-S protein or anti-receptor-binding domain (RBD) antibody titers, and the cellular immunoreaction, as assessed by antigen-induced IFN{gamma} expression, were up-regulated. In IgG subclass analysis, IgG2b was induced as the main subclass. Based on these analyses, DNA vaccine with alum adjuvant preferentially induced Th1-type T cell polarization. We confirmed the neutralizing action of DNA vaccine-induced antibodies via two different methods, a binding assay of RBD recombinant protein with angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, and pseudovirus assay. Further B cell epitope mapping analysis using a peptide array showed that most vaccine-induced antibodies recognized the S2 and RBD subunits, but not the S1 subunit. In conclusion, DNA vaccine targeting the spike glycoprotein of SARS-CoV-2 might be an effective and safe approach to combat the COVID-19 pandemic.
RESUMO
BACKGROUND: Nuclear factor-kappaB (NF-kappaB) plays a pivotal role in restenosis after percutaneous coronary intervention (PCI) and the aim of the present clinical trials was to evaluate the effectiveness of a NF-kappaB decoy for preventing restenosis. METHODS AND RESULTS: The initial case was a patient suffering from effort angina who had stenoses in the proximal and middle portions of the right coronary artery. The patient received 2 stents; the NF-kappaB decoy was delivered to the distal site, but not the proximal site. Six months after the PCI, the NF-kappaB decoy had suppressed restenosis in comparison with the no-decoy transfection site. The second case was a patient who underwent single-stent insertion and decoy transfection at the same site, and minimal intimal thickening was observed at 6 month after PCI. No systemic adverse effects were observed in either case. CONCLUSIONS: These results indicate the clinical usefulness and safety of NF-kappaB decoy transfection after PCI, but further evaluations are necessary to confirm its clinical effectiveness.
