State Key Laboratory for Molecular Virology and Genetic Engineering, Biotech Center for Viral Disease Emergency, National Institute for Viral Disease Control and Prevention, China CDC, Changpingqu, Beijing 102206, China.
Virol J. 2011 Jun 15;8:302. doi: 10.1186/1743-422X-8-302.
Persistent infection with high-risk human papillomavirus (HPV) is a predominant cause of cervical cancer, and HPV16 and HPV18 occur in 50% and 20% of cervical cancer cases, respectively. The viral oncogenes E6 and E7 are constitutively expressed by HPV-associated tumour cells and can therefore be used as target antigens for immunotherapy. In this study, we constructed a recombinant vaccinia virus co-expressing the HPV16/18 E7E6 fusion proteins (rVVJ16/18E7E6) for use as a therapeutic vaccine for the treatment of HPV16⁺ and HPV18⁺ cancers.
We constructed a bivalent recombinant vaccinia virus expressing modified E7E6 fusion proteins of HPV type 16 and 18 (rVVJ16/18E7E6) based on the vaccinia virus Tiantan strain. We then defined the cellular immune responses to the virus in mice and rhesus monkeys and assessed antitumour efficacy of these responses in mice using the TC-1 tumour challenge model.
Our data demonstrated that rVVJ16/18E7E6 was able to elicit varying levels of CD8⁺ T cell immune responses and lysis of target cells in mice in response to peptides HPV16E7₄₉₋₅₇ and HPV18E6₆₇₋₇₅. Furthermore, the virus was also able to induce anti-tumour responses in the HPV16⁺ TC-1 tumour challenge model, including partial protection (30-40%) and delayed tumour appearance. In addition, the virus was able to induce immune responses in rhesus monkeys.
The recombinant vaccinia virus rVVJ16/18E7E6 can generate clear and significant cellular immunity in both mice and rhesus monkeys. These data provide a basis for the use of this recombinant virus as a potential vaccine candidate for further study.
高危型人乳头瘤病毒（HPV）持续感染是宫颈癌的主要病因，HPV16 和 HPV18 分别占宫颈癌病例的 50%和 20%。HPV 相关肿瘤细胞持续表达病毒致癌基因 E6 和 E7，因此可作为免疫治疗的靶抗原。本研究构建了共表达 HPV16/18 E7E6 融合蛋白的重组痘苗病毒（rVVJ16/18E7E6），作为治疗 HPV16⁺和 HPV18⁺癌症的治疗性疫苗。
我们基于天坛株痘苗病毒构建了表达 HPV 型 16 和 18 改良 E7E6 融合蛋白的双价重组痘苗病毒（rVVJ16/18E7E6）。然后，我们在小鼠和恒河猴中定义了针对该病毒的细胞免疫反应，并使用 TC-1 肿瘤挑战模型评估了这些反应的抗肿瘤功效。
我们的数据表明，rVVJ16/18E7E6 能够在小鼠中诱导针对 HPV16E7₄₉₋₅₇ 和 HPV18E6₆₇₋₇₅ 肽的不同水平的 CD8⁺T 细胞免疫反应和靶细胞裂解。此外，该病毒还能够在 HPV16⁺TC-1 肿瘤挑战模型中诱导抗肿瘤反应，包括部分保护（30-40%）和肿瘤出现延迟。此外，该病毒还能够在恒河猴中诱导免疫反应。
重组痘苗病毒 rVVJ16/18E7E6 能够在小鼠和恒河猴中产生明显的细胞免疫反应。这些数据为进一步研究该重组病毒作为潜在疫苗候选物提供了依据。
