Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
The 3rd Clinical Department, China Medical University, Shenyang, China.
Int Immunopharmacol. 2018 Mar;56:249-260. doi: 10.1016/j.intimp.2018.01.037. Epub 2018 Feb 3.
Cell mediated immune (CMI) responses are crucial for the clearance of human papillomavirus (HPV) infection and HPV-associated lesions. Activated CD8 T cells are critical effector cells in recognizing and killing HPV-infected or HPV-transformed cells. CD4 T cells provide help for priming the generation and maintenance of CD8 T cells as well as for tumors immunity. An ideal therapeutic HPV peptide-based vaccine should induce both a robust CD8 T-cell response as well as a CD4 T-cell response for ensuring their efficiency. Candida skin test reagent was demonstrated to be able to induce the secretion of IL-12 by Langerhans cells and T-cell proliferation in vitro by our group, which indicated the potential of Candida to enhance CMI response. In this current study, we designed a novel HPV peptide-based vaccine which includes HPV16 E7 peptides and Candida as an adjuvant. The immune responses induced by the vaccine were comprehensively evaluated. The results showed that the vaccine induced significant HPV-specific CD8 T-cell and Th1 CD4 T-cell responses as well as humoral immune response. It is interesting that Candida alone induced a significant polarization of Th1 response an production of IFN-γ, which indicated Candida alone may be used as a potential immunotherapeutic reagent not only for HPV-associated lesions but also for other viral infection or even cancers.
细胞介导的免疫(CMI)反应对于清除人乳头瘤病毒(HPV)感染和 HPV 相关病变至关重要。激活的 CD8 T 细胞是识别和杀死 HPV 感染或 HPV 转化细胞的关键效应细胞。CD4 T 细胞为产生和维持 CD8 T 细胞以及肿瘤免疫提供帮助。理想的治疗性 HPV 肽疫苗应能诱导强烈的 CD8 T 细胞反应和 CD4 T 细胞反应,以确保其效率。我们小组的研究表明,白色念珠菌皮肤试验试剂能够在体外诱导朗格汉斯细胞分泌 IL-12 和 T 细胞增殖,这表明白色念珠菌具有增强 CMI 反应的潜力。在本研究中,我们设计了一种新型的 HPV 肽疫苗,其中包括 HPV16 E7 肽和白色念珠菌作为佐剂。全面评估了疫苗诱导的免疫反应。结果表明,该疫苗诱导了显著的 HPV 特异性 CD8 T 细胞和 Th1 CD4 T 细胞反应以及体液免疫反应。有趣的是,白色念珠菌单独诱导了显著的 Th1 反应和 IFN-γ的产生,这表明白色念珠菌不仅可作为 HPV 相关病变的潜在免疫治疗试剂,还可作为其他病毒感染甚至癌症的潜在免疫治疗试剂。