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Hooman Kaghazian
Zohre Eftekhari
Seyed Dawood Mousavi Nasab
Ruhollah Dorostkar
Ali Akbar Pourfathollah
Mahyar Jeloudai Mamaghani
Seyed Mehdi Hassanzadeh


COVID-19, toxicology, COVID-19 Vaccines, Vaccine


Background: This study aimed to evaluate the outcomes of preclinical studies on the safety and immunogenicity of an inactivated COVID-19 vaccine candidate to warrant further clinical evaluation.

Methods: SARS-CoV-2 positive nasopharyngeal swab specimens were confirmed by real-time polymerase chain reaction and next-generation sequencing. The safety and immunogenicity tests of the COVID-19 vaccine were carried out in rats and Rhesus monkeys, and Balb/C mice and Rhesus monkeys, respectively.

 Results: The candidate vaccine was well tolerated and induced promising levels of SARS-CoV-2–specific IgG1, IgG2a, and Granzyme B in Balb/C mice, and anti-SARS-CoV-2 spike IgG and neutralizing antibodies in Rhesus monkeys. Based on cVNT results, the inactivated vaccine in 0.5 and 1 µg/100 µL doses was able to induce a neutralizing effect against the SARS-CoV-2 virus up to a dilution of 1:512 and 1:1000. The protective efficacy of the vaccine candidate was challenged with 2 ×108 PFU of live viruses and confirmed by lung CT scan and histopathological evaluations compared to the control group. Repeated intramuscular injection of the candidate vaccine was generally well-tolerated in Rats and Rhesuses. No significant side effects were observed in rats injected with ten full human doses and in the Rhesus monkeys with three full human doses.

 Conclusion: Based on the findings presented in this study, it is recommended that this vaccine be moved into human testing commencing with a phase I clinical trial.

Keywords: immunogenicity, toxicology, vaccine

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