SARS-CoV-2 Delta Inactivated Vaccine: Safety Assessment in Sprague Dawley Rats and Cynomolgus Monkeys

Abstract

Developing a reliable and safe SARS-CoV-2 vaccine is essential to halt the COVID-19 pandemic. Preclinical studies are designed to evaluate vaccine safety. Testing vaccine toxicity in animals helps predict safety in humans, thereby reducing risks during human use and providing a foundation for clinical trial design. This study aimed to (1) provide a reference for clinical research by assessing the toxicity of a SARS-CoV-2 inactivated vaccine (Vero cell line, Delta strain B.1.617.2) following six weeks of repeated intramuscular injections, and (2) evaluate the acute toxicity of the vaccine in Sprague-Dawley rats over 14 days after a single intramuscular injection. Repeated intramuscular injections in cynomolgus monkeys revealed elevated body temperature, eosinophils, fibrillation, and cytokine IL-6 levels after the first and/or last injection, with no evident systemic damage; five doses per monkey were deemed safe. Injection site irritation was observed at one and five doses per monkey, with recovery noted after four weeks. High levels of specific IgG antibodies against the S1 protein were detected in all animals. These findings suggest the vaccine is safe and support progression to human phase I clinical trials. Additionally, this study provides a protocol for developing a preclinical evaluation system for next-generation SARS-CoV-2 vaccines.