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

Autor: Oh S; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-Ro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Jang MS; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-Ro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Jung KJ; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-Ro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Han JS; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-Ro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Lee H; GeneOne Life Science, Inc., Yeongdeungpo Gu, Seoul, 07335, Korea., Gil A; GeneOne Life Science, Inc., Yeongdeungpo Gu, Seoul, 07335, Korea., Jeon B; GeneOne Life Science, Inc., Yeongdeungpo Gu, Seoul, 07335, Korea., Roberts CC; GeneOne Life Science, Inc., Yeongdeungpo Gu, Seoul, 07335, Korea., Maslow JN; GeneOne Life Science, Inc., Yeongdeungpo Gu, Seoul, 07335, Korea., Kim YB; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-Ro, Yuseong-Gu, Daejeon, 34114, Republic of Korea., Han KH; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-Ro, Yuseong-Gu, Daejeon, 34114, Republic of Korea. hankh@kitox.re.kr.
Jazyk: angličtina
Zdroj: Archives of toxicology [Arch Toxicol] 2023 Apr; Vol. 97 (4), pp. 1177-1189. Date of Electronic Publication: 2023 Jan 23.
DOI: 10.1007/s00204-023-03446-y
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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