Development, analysis, and preclinical evaluation of inactivated vaccine candidate for prevention of Covid-19 disease

Abstract

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the sprawling capital of Central China’s Hubei province Wuhan in 2019. Since late 2019, SARS-CoV-2 has been responsible for a global pandemic that has resulted in 405,961,201 confirmed cases of infection and 5,789,567 deaths as of February 11, 2022, according to the World Health Organization (WHO). Here we report the development of an inactivated SARS-CoV-2 vaccine candidate and show that its efficacy and safety in preclinical studies warrant further clinical evaluation. Efficiency and possible side effects of vaccine candidate on different doses were evaluated using histopathology, K18 hACE2 transgenic mice challenge, T-cell response, and serum neutralization test in Balb/c mice. All pilot production and propagation experiments of SARS-CoV-2 were performed in the Level 3 Negative Pressure Biosafety Facility (BSL3/ABSL-3) according to COVID-19 interim guidance of WHO. All analytical studies have shown that the quality control parameters of the vaccine candidate meet the requirements for inactivated viral vaccines according to European Pharmacopeia. The vaccine candidate (KOCAK-19) has been authorized by the Turkish Medicines and Medical Devices Agency and has now entered phase 2 clinical development (NCT04838080). Abbreviations: SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2.; MERS-CoV: Middle East Respiratory Syndrome Coronavirus.; qRT-PCR: Quantitative Real-Time Polymerase Chain Reaction.; TEM: Transmissible Electron Microscopy.; SEC: Size Exclusion.; AEX: Anion exchange.; BPL: β-Propiolactone.; CPE: Cytopathic Effect.; TCID50: 50% Tissue Culture Infectious Dose.; hACE-2: Human Angiotensin-Converting Enzyme 2.; mRNA: Messenger RNA.; RBD: Receptor binding domain.; Nab: Neutralizing antibody.; MOI: Multiply of Infection. HIGHLIGHTS A new inactivated vaccine candidate to protect against COVID −19 SARS-CoV-2 inactive vaccine development in disposable wave bioreactor systems with microcarrier technologies and analytical analysis Preclinical toxicity and immunity trials for COVID-19 inactive vaccine candidate in Balb/c mice, K18 transgenic mice and, ferrets.

Keywords

• sars-cov-2
• inactivated vaccines
• tem analysis
• microcarrier
• histopathology
• preclinical trials