Comprehensive review of preclinical evaluation strategies for COVID-19 vaccine candidates: assessing immunogenicity, toxicology, and safety profiles.

Following the worldwide spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a vital requirement for safe and effective vaccines against Coronavirus disease 2019 (COVID-19). Therefore, several vaccine-candidate platforms have been designed, tested, and developed. Based on guidelines, preclinical studies are recommended to assess the safety and potency of COVID-19 vaccines in appropriate in vitro and in vivo settings. These studies provide essential information to describe the potential toxic properties of a vaccine and the formulation of vaccine agents during the preclinical trial phase. In toxicology studies, several factors must be considered, such as the appropriate animal species and strains, dosing timetable, mode of administration, time of sampling for biochemistry and antibody evaluation, and necropsy. Pharmacokinetic/ biodistribution studies are not usually required for infectious disease prophylaxis vaccines unless the vaccine contains a novel substance. Evaluating their biodistribution is crucial for newly developed vaccines, such as lipid nanoparticles -messenger RNA (LNP-mRNA), DNA, and Viral vectors in non-replicated (VVnr), or recombinant virus vaccines. The review highlights the importance of preclinical studies in assessing the safety and efficacy of vaccine candidates. This guidance is essential for researchers and manufacturers to design effective vaccines that can progress to clinical trials safely.