Sun Zhongjie, Wu Zhongyan, Su Xuncheng
State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Newish Biological R&D Center, Wuxi 214111, China.
Vaccines (Basel). 2025 Jan 9;13(1):49. doi: 10.3390/vaccines13010049.
Human papillomavirus (HPV) is a prevalent infection affecting both men and women, leading to various cytological lesions. Therapeutic vaccines mount a HPV-specific CD8+ cytotoxic T lymphocyte response, thus clearing HPV-infected cells. However, no therapeutic vaccines targeting HPV are currently approved for clinical treatment due to limited efficacy. Our goal is to develop a vaccine that can effectively eliminate tumors caused by HPV.
We genetically fused the chemokine XCL1 with the E6 and E7 proteins of HPV16 to target cDC1 and enhance the vaccine-induced cytotoxic T cell response, ultimately developing a DNA vaccine. Additionally, we screened various interleukins and identified IL-9 as an effective molecular adjuvant for our DNA vaccine.
The fusion of Xcl1 significantly improved the quantity and quality of the specific CD8+ T cells. The fusion of Xcl1 also increased immune cell infiltration into the tumor microenvironment. The inclusion of IL-9 significantly elevated the vaccine-induced specific T cell response and enhanced anti-tumor efficacy. IL-9 promotes the formation of central memory T cells.
the fusion of Xcl1 and the use of IL-9 as a molecular adjuvant represent promising strategies for vaccine development.
人乳头瘤病毒（HPV）是一种常见感染，影响男性和女性，可导致各种细胞学病变。治疗性疫苗引发针对HPV的CD8 + 细胞毒性T淋巴细胞反应，从而清除HPV感染的细胞。然而，由于疗效有限，目前尚无针对HPV的治疗性疫苗被批准用于临床治疗。我们的目标是开发一种能够有效消除由HPV引起的肿瘤的疫苗。
我们将趋化因子XCL1与HPV16的E6和E7蛋白进行基因融合，以靶向cDC1并增强疫苗诱导的细胞毒性T细胞反应，最终开发出一种DNA疫苗。此外，我们筛选了各种白细胞介素，并确定IL-9是我们DNA疫苗的有效分子佐剂。
Xcl1的融合显著提高了特异性CD8 + T细胞的数量和质量。Xcl1的融合还增加了免疫细胞向肿瘤微环境的浸润。加入IL-9显著提高了疫苗诱导的特异性T细胞反应并增强了抗肿瘤疗效。IL-9促进中枢记忆T细胞的形成。
Xcl1的融合以及使用IL-9作为分子佐剂是疫苗开发的有前景的策略。
