Genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc vaccine against SARS-CoV-2 in Sprague-Dawley rats and Beagle dogs.

Autor: Park SJ; Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Park H; Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Back SM; Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Lee YJ; Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Seo JW; Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Kim D; Sumagen Co., Ltd, 4F Dongwon Building, Teheran-Ro 77-Gil, Gangnam-Gu, Seoul, 06159, Republic of Korea., Lee JH; Sumagen Co., Ltd, 4F Dongwon Building, Teheran-Ro 77-Gil, Gangnam-Gu, Seoul, 06159, Republic of Korea., Kwak C; Sumagen Co., Ltd, 4F Dongwon Building, Teheran-Ro 77-Gil, Gangnam-Gu, Seoul, 06159, Republic of Korea., Han KH; Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Son HY; College of Veterinary Medicine, Chungnam National University, 99 Daehak-Ro, Yuseong-Gu, Daejeon, 34131, Republic of Korea., Kim YB; Korea Institute of Toxicology, 141 Gaejeongro, Yuseong-Gu, Daejeon, 34114, Republic of Korea. ybkim@kitox.re.kr.
Jazyk: angličtina
Zdroj: Archives of toxicology [Arch Toxicol] 2024 Jul; Vol. 98 (7), pp. 2185-2197. Date of Electronic Publication: 2024 Apr 12.
DOI: 10.1007/s00204-024-03746-x
Abstrakt: The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic, prompting rapid vaccine development. Although vaccines are effective, the occurrence of rare adverse events following vaccination highlights the necessity of determining whether the benefits outweigh the risks posed by the infection itself. The recombinant Vesicular Stomatitis Virus (rVSV) platform is a promising vector for vaccines against emerging viruses. However, limited studies have evaluated the genotoxicity and safety pharmacology of this viral vector vaccine, which is crucial to ensure the safety of vaccines developed using this platform. Hence, the present study aimed to assess the genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc COVID-19 vaccine using micronucleus and comet assays, as well as neurobehavioral, body temperature, respiratory, and cardiovascular assessments in Sprague-Dawley rats and beagle dogs. The intramuscular administration of rVSVInd(GML)-mspSGtc at doses up to 1.5 × 10 9 PFU/animal did not increase the number of bone marrow micronucleated polychromatic erythrocytes or cause liver DNA damage. Additionally, it had no significant impact on neurobehavioral functions in rats and showed marginal temporary changes in body temperature, respiratory rate, heart rate, and electrocardiogram parameters in rats and dogs, all of which resolved within 24 h. Overall, following genotoxicity and pharmacological safety assessments, rVSVInd(GML)-mspSGtc displayed no notable systemic adverse effects in rats and dogs, suggesting its potential as a vaccine candidate for human clinical trials.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: