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新型冠状病毒 DNA 疫苗候选物 pGO-1002 在新西兰白兔皮内注射的临床前安全性评估。

Preclinical safety assessment of the suction-assisted intradermal injection of the SARS-CoV-2 DNA vaccine candidate pGO-1002 in white rabbit.

机构信息

Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-Ro, Yuseong-Gu, Daejeon, 34114, Republic of Korea.

GeneOne Life Science, Inc., Yeongdeungpo Gu, Seoul, 07335, Korea.

出版信息

Arch Toxicol. 2023 Apr;97(4):1177-1189. doi: 10.1007/s00204-023-03446-y. Epub 2023 Jan 23.

Abstract

pGO-1002, a non-viral DNA vaccine that expresses both spike and ORF3a antigens of SARS-CoV-2, is undergoing phase 1 and phase 2a clinical trials in Korea and the US. A preclinical repeated-dose toxicity study in New Zealand white rabbits in compliance with Good Laboratory Practice (GLP) was conducted to assess the potential toxicity, local tolerance, and immunogenicity of the vaccine and GeneDerm suction device. The dose rate was 1.2 mg/head pGO-1002, and this was administered intradermally to a group of animals (eight animals/sex/group) three times at 2-week intervals, followed by a 4-week recovery period. After each administration, suction was applied to the injection site using the GeneDerm device. Mortality, clinical signs, body weight, food consumption, skin irritation, ophthalmology, body temperature, urinalysis, and clinical pathology were also monitored. Gross observations and histopathological evaluation were performed. Overall, pGO-1002 administration-related changes were confined to minor damage or changes at the injection site, increased spleen weight and minimal increased cellularity in white pulp. All changes of injection site were considered local inflammatory changes or pharmacological actions due to the vaccine with the changes in spleen considered consistent with vaccine-induced immune activation. All findings showed reversibility during the 4-week recovery period. Animals vaccinated with pGO-1002, administered by intradermal injection and followed by application of suction with GeneDerm, developed humoral and cellular responses against the SARS-CoV-2 antigens consistent with prior studies in rats. Collectively, it was concluded that the pGO-1002 vaccine was safe and effective under these experimental conditions and these data supported future human study of the vaccine, now known as GLS-5310, for clinical trial use.

摘要

pGO-1002 是一种非病毒 DNA 疫苗,可表达 SARS-CoV-2 的刺突蛋白和 ORF3a 抗原,目前正在韩国和美国进行 1 期和 2a 期临床试验。为评估疫苗和 GeneDerm 抽吸装置的潜在毒性、局部耐受性和免疫原性,按照良好实验室规范(GLP)在新西兰白兔中进行了重复剂量毒性预临床研究。剂量率为 1.2mg/头 pGO-1002,每 2 周皮内给药一次,共 3 次,然后进行 4 周恢复期。每次给药后,使用 GeneDerm 装置在注射部位进行抽吸。还监测了死亡率、临床症状、体重、食物消耗、皮肤刺激、眼科、体温、尿液分析和临床病理学。进行了大体观察和组织病理学评估。总体而言,pGO-1002 给药相关变化仅限于注射部位的轻微损伤或变化、脾脏重量增加和白髓细胞轻度增加。所有注射部位的变化都被认为是局部炎症变化或疫苗的药理学作用,因为脾脏的变化被认为与疫苗诱导的免疫激活一致。所有发现都在 4 周恢复期内具有可逆性。经皮内注射 pGO-1002 并随后用 GeneDerm 进行抽吸的动物对 SARS-CoV-2 抗原产生了体液和细胞反应,与先前在大鼠中进行的研究一致。总之,在这些实验条件下,pGO-1002 疫苗是安全有效的,这些数据支持了该疫苗(现称为 GLS-5310)用于临床试验的人体研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9491/9868498/7d9fd4d958ab/204_2023_3446_Fig1_HTML.jpg

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