Abstract
The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials.
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The data that support the findings of this study are available from HuVet bio, Inc. but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of HuVet bio, Inc.
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Acknowledgements
This research was financially supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT of Korean government (Nos. 2020M3A9I2108860 and 2022M3A9J21081348). The funding sources were not involved in any step of the study, that is, design, collection, analysis, data interpretation, or writing of the manuscript.
Funding
This research was financially supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT of Korean government (Nos. 2020M3A9I2108860 and 2022M3A9J21081348). The funding sources were not involved in any step of the study, that is, design, collection, analysis, data interpretation, or writing of the manuscript.
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S-JP was responsible for result analysis and preparation of the manuscript. MSJ, K-HL, and J‐WS carried out the animal study. W-JI performed autopsies and histopathology exams as a pathologist. Kang-Hyun Han designed the study. S-EK designed the study and was responsible for formulation and analysis. EJ was responsible for culture processes. DP and Y-BK caried out investigations, supervision and writing review and editing. All authors read and approved the final manuscript.
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Park, SJ., Jang, M.S., Lim, KH. et al. Preclinical evaluation of general toxicity and safety pharmacology of a receptor-binding domain-based COVID-19 subunit vaccine in various animal models. Arch Toxicol 97, 2429–2440 (2023). https://doi.org/10.1007/s00204-023-03549-6
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DOI: https://doi.org/10.1007/s00204-023-03549-6