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

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 (4g, 6g, and 8g), followed by exposure to SARS-CoV-2.Utilising 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 emphasise 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 localised inflammatory responses.The vaccinated groups showed less testicular atrophy, highlighting the vaccine's protective role in reproductive health.The study underlines optimising 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.