Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran; School of Allied Medical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran.
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Microb Pathog. 2019 Jul;132:20-25. doi: 10.1016/j.micpath.2019.04.028. Epub 2019 Apr 17.
Various promising procedures have been used to improve the potency of DNA vaccines for the treatment of human papillomavirus type 16 (HPV16) infections. Interleukin-12 (IL12) is a powerful adjuvant that can contribute to T cell-mediated protection against many pathogens, specifically viruses. Considering the important role of T cell-mediated immunity in tumor clearance, the induction of these responses can help control the progression of tumors in animal models. We have demonstrated that the co-administration of codon-optimized E7 (uE7) gene of HPV16 with interleukin-12 is effective in the development of antitumor responses.
The present study examined the co-administration of codon-optimized HPV16 E7 gene with murine interleukin-12 gene (mIL-12) as a vaccine adjuvant in tumor mice model.
C57BL/6 mice were studied for tumor progression after injection of recombinant DNA vaccines. Lactate dehydrogenase (LDH) and IFN-γ were measured to evaluate the activity of cytotoxic T lymphocytes (CTLs). Measurements of tumor volume and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay were used for assessment of therapeutic antitumor effects of the vaccines.
Results showed that DNA vaccines, specifically codon-optimized E7/murine interleukin-12 (mIL-12), elicited significant differences in levels of IFN-γ and cytotoxic T lymphocyte (CTLs) responses compared to control groups. Furthermore, higher antitumor response and lower tumor size in the vaccine group was significantly evident compared to control group.
The co-administration of codon-optimized HPV16 E7 gene with IL12 significantly enhances the DNA vaccine potency against HPV16-associated cervical cancer.
为了提高治疗人乳头瘤病毒 16 型（HPV16）感染的 DNA 疫苗的效力，已经采用了多种有前途的方法。白细胞介素-12（IL12）是一种强大的佐剂，可以促进针对多种病原体，特别是病毒的 T 细胞介导的保护。鉴于 T 细胞介导的免疫在肿瘤清除中的重要作用，诱导这些反应有助于控制动物模型中肿瘤的进展。我们已经证明，共施用 HPV16 的密码子优化 E7（uE7）基因与白细胞介素-12 可有效诱导抗肿瘤反应。
本研究探讨了共施用密码子优化的 HPV16 E7 基因与鼠白细胞介素-12 基因（mIL-12）作为疫苗佐剂在肿瘤小鼠模型中的作用。
研究了 C57BL/6 小鼠在注射重组 DNA 疫苗后肿瘤进展情况。通过测量乳酸脱氢酶（LDH）和 IFN-γ 来评估细胞毒性 T 淋巴细胞（CTL）的活性。通过测量肿瘤体积和 MTT[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐]测定法来评估疫苗的治疗抗肿瘤作用。
结果表明，与对照组相比，DNA 疫苗，特别是密码子优化的 E7/鼠白细胞介素-12（mIL-12），可显著提高 IFN-γ 和细胞毒性 T 淋巴细胞（CTL）反应水平。此外，与对照组相比，疫苗组的抗肿瘤反应更高，肿瘤体积更小。
共施用 HPV16 E7 基因与 IL12 可显著增强针对 HPV16 相关宫颈癌的 DNA 疫苗效力。
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