Immunogenicity and protection efficacy of a COVID-19 DNA vaccine encoding spike protein with D614G mutation and optimization of large-scale DNA vaccine production.

Autor: Gül A; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Bioengineering, Faculty of Engineering, Ege University, İzmir, Türkiye.; Department of Bioengineering, Graduate School of Natural and Applied Sciences, Ege University, İzmir, Türkiye., Erkunt Alak S; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Biology, Molecular Biology Section, Faculty of Science, Ege University, İzmir, Türkiye., Can H; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Biology, Molecular Biology Section, Faculty of Science, Ege University, İzmir, Türkiye.; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye., Karakavuk M; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye.; Ödemiş Vocational School, Ege University, İzmir, Türkiye., Korukluoğlu G; Republic of Türkiye, General Directorate of Public Health, Ministry of Health, National Virology Reference Central Laboratory, Ankara, Türkiye.; Department of Medical Microbiology, Ankara Bilkent City Hospital, University of Health Sciences, Ankara, Türkiye., Altaş AB; Republic of Türkiye, General Directorate of Public Health, Ministry of Health, National Virology Reference Central Laboratory, Ankara, Türkiye., Gül C; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Biotechnology, Graduate School of Natural and Applied Sciences, Ege University, İzmir, Türkiye., Karakavuk T; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Biotechnology, Graduate School of Natural and Applied Sciences, Ege University, İzmir, Türkiye., Köseoğlu AE; Department of Biology, Molecular Biology Section, Faculty of Science, Ege University, İzmir, Türkiye.; Department of Environmental Microbiology and Biotechnology, Faculty of Chemistry, Duisburg-Essen University, Essen, Germany., Ülbeği Polat H; TÜBİTAK Marmara Research Center, Vice Presidency of Life Sciences, Kocaeli, Türkiye., Yazıcı Malkoçoğlu H; TÜBİTAK Marmara Research Center, Vice Presidency of Life Sciences, Kocaeli, Türkiye., Taş Ekiz A; TÜBİTAK Marmara Research Center, Vice Presidency of Life Sciences, Kocaeli, Türkiye., Abacı İ; TÜBİTAK Marmara Research Center, Vice Presidency of Life Sciences, Kocaeli, Türkiye., Aksoy Ö; TÜBİTAK Marmara Research Center, Vice Presidency of Life Sciences, Kocaeli, Türkiye., Enül H; Pendik Veterinary Control Institute, İstanbul, Türkiye., Adıay C; Pendik Veterinary Control Institute, İstanbul, Türkiye., Uzar S; Pendik Veterinary Control Institute, İstanbul, Türkiye., Saraç F; Pendik Veterinary Control Institute, İstanbul, Türkiye., Ün C; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Biology, Molecular Biology Section, Faculty of Science, Ege University, İzmir, Türkiye.; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye., Gürüz AY; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye.; Department of Parasitology, Faculty of Medicine, Ege University, İzmir, Türkiye., Kantarcı AG; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye.; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, İzmir, Türkiye., Akbaba H; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye.; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, İzmir, Türkiye., Erel Akbaba G; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, İzmir Katip Çelebi University, İzmir, Türkiye., Yılmaz H; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Trakya University, Edirne, Türkiye., Değirmenci Döşkaya A; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye.; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye.; Department of Parasitology, Faculty of Medicine, Ege University, İzmir, Türkiye., Taşbakan M; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye.; Department of Infectious Diseases, Faculty of Medicine, Ege University, İzmir, Türkiye., Pullukçu H; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye.; Department of Infectious Diseases, Faculty of Medicine, Ege University, İzmir, Türkiye., Karasulu E; Ege University Research and Application Center of Drug Development and Pharmacokinetics, İzmir, Türkiye., Tekin Ş; Department of Basic Medical Sciences, Medical Biology, Faculty of Medicine, University of Health Sciences, İstanbul, Türkiye., Döşkaya M; Vaccine Development Application and Research Center, Ege University, 35100, İzmir, Türkiye. mert.doskaya@ege.edu.tr.; Department of Vaccine Studies, Institute of Health Sciences, Ege University, İzmir, Türkiye. mert.doskaya@ege.edu.tr.; Department of Parasitology, Faculty of Medicine, Ege University, İzmir, Türkiye. mert.doskaya@ege.edu.tr.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jun 15; Vol. 14 (1), pp. 13865. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1038/s41598-024-64690-5
Abstrakt: Severe acute respiratory syndrome coronavirus 2 had devastating consequences for human health. Despite the introduction of several vaccines, COVID-19 continues to pose a serious health risk due to emerging variants of concern. DNA vaccines gained importance during the pandemic due to their advantages such as induction of both arms of immune response, rapid development, stability, and safety profiles. Here, we report the immunogenicity and protective efficacy of a DNA vaccine encoding spike protein with D614G mutation (named pcoSpikeD614G) and define a large-scale production process. According to the in vitro studies, pcoSpikeD614G expressed abundant spike protein in HEK293T cells. After the administration of pcoSpikeD614G to BALB/c mice through intramuscular (IM) route and intradermal route using an electroporation device (ID + EP), it induced high level of anti-S1 IgG and neutralizing antibodies (P < 0.0001), strong Th1-biased immune response as shown by IgG2a polarization (P < 0.01), increase in IFN-γ levels (P < 0.01), and increment in the ratio of IFN-γ secreting CD4 + (3.78-10.19%) and CD8 + (5.24-12.51%) T cells. Challenging K18-hACE2 transgenic mice showed that pcoSpikeD614G administered through IM and ID + EP routes conferred 90-100% protection and there was no sign of pneumonia. Subsequently, pcoSpikeD614G was evaluated as a promising DNA vaccine candidate and scale-up studies were performed. Accordingly, a large-scale production process was described, including a 36 h fermentation process of E. coli DH5α cells containing pcoSpikeD614G resulting in a wet cell weight of 242 g/L and a three-step chromatography for purification of the pcoSpikeD614G DNA vaccine.
(© 2024. The Author(s).)
Databáze: MEDLINE
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