Herd Karen A, Harvey Tracey, Khromykh Alexander A, Tindle Robert W
Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, and Clinical Medical Virology Centre, University of Queensland, Brisbane, Australia.
Virology. 2004 Feb 20;319(2):237-48. doi: 10.1016/j.virol.2003.10.032.
The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses.
在人乳头瘤病毒（HPV）相关的宫颈癌中，E7癌蛋白在转化细胞中的持续存在提供了一种肿瘤特异性抗原，免疫治疗策略可针对该抗原。最近有报道称，源自黄病毒库京（KUN）的自我复制RNA（复制子）疫苗载体可诱导T细胞免疫。在此，我们报告将HPV16 E7蛋白的一个CTL表位纳入由KUN载体编码的多表位中，可诱导针对E7的T细胞反应，并保护小鼠免受表达E7的上皮肿瘤的攻击。我们发现，包装在病毒样颗粒中的复制子RNA比裸复制子RNA或构建用于在体内转录复制子RNA的质粒DNA更有效。尽管E7 CTL表位在多表位中其他CTL表位的背景下是次显性的，但仍诱导了保护性免疫。结果证明了KUN复制子载体系统在诱导针对病毒编码的人类肿瘤特异性抗原的保护性免疫以及诱导多表位CTL反应方面的有效性。
