Dose-Dependent Effects and Safety Assessment of Inactivated COVID-19 Vaccine: A Comprehensive Preclinical Study


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SÖNMEZ K., Onen E. A., Bamac Ö., YILDIRIM F., Bezawada S., AVANUS K., ...Daha Fazla

PAKISTAN VETERINARY JOURNAL, cilt.45, sa.2, ss.605-617, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 45 Sayı: 2
  • Basım Tarihi: 2025
  • Doi Numarası: 10.29261/pakvetj/2025.163
  • Dergi Adı: PAKISTAN VETERINARY JOURNAL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.605-617
  • Anahtar Kelimeler: Histopathology, Inactivated SARS-CoV-2, K18 hACE2, Transgenic mice, vaccine
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Currently, researchers are working to develop new vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causative agent of COVID-19. This study assesses the effectiveness and safety of the inactivated SARS-CoV-2 vaccine candidate KOCAK-19 in Balb/c and K18 hACE2 transgenic mice. Different groups of mice were administered varying doses of the vaccine (4 mu g, 6 mu g, and 8 mu g), followed by exposure to SARS-CoV-2. Utilizing two distinct mouse models allowed for a thorough evaluation of both general immune responses (Balb/c) and human-like susceptibility to SARS-CoV-2 (K18 hACE2), enhancing the findings' relevance. Statistical analysis was conducted using the Kruskal-Wallis and Dunn's tests, with significance at P<0.05. The results emphasize the protective effects of vaccination against severe lung injury, vascular damage, and testicular atrophy. KOCAK-19 vaccination significantly decreases tracheal epithelial hyperplasia, vascular injury, perivascular lymphoid infiltration, microthrombosis, and severe haemorrhage. However, higher vaccine doses are linked to increased bronchial hyperplasia, excessive secretion, and localized inflammatory responses. The vaccinated groups showed less testicular atrophy, highlighting the vaccine's protective role in reproductive health. The study underlines optimizing vaccine dosages to balance immune protection and potential adverse effects. These results offer important preclinical data to improve inactivated vaccine formulations, aiding the development of safer and more effective COVID-19 vaccination strategies.