Department of Medical Pharmacology, Università di Milano, Milan, Italy.
J Transl Med. 2010 Apr 21;8:40. doi: 10.1186/1479-5876-8-40.
Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions.
Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP) recombinants separately expressing the HPV-16 E6 (FPE6) and E7 (FPE7) transgenes were used for priming, followed by E7 protein boosting.
All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals.
These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication.
每年约有 50 万例新的宫颈癌病例发生，因此开发针对 HPV 的有效治疗性疫苗成为当务之急。由于 HPV-16 肿瘤细胞中均表达 E6 和 E7 癌蛋白，因此表达这些蛋白的疫苗可能清除已建立的肿瘤，并支持 HPV 相关癌前病变的治疗。
在兔的临床前试验中，测试了三种不同的免疫方案，以评估 HPV-16 疫苗的体液和细胞介导反应。分别表达 HPV-16 E6（FPE6）和 E7（FPE7）转基因的禽痘病毒（FP）重组体用于初级免疫，随后进行 E7 蛋白加强免疫。
所有方案均能有效引起高抗体反应。这也通过白细胞介素-4 的产生得到证实，同时用 FPE6 和 FPE7 进行初级免疫以及 E7 蛋白加强免疫后，白细胞介素-4 的产生增加。大多数动物也检测到细胞介导的免疫反应。
这些结果为联合使用禽痘病毒重组体的治疗建立了初步概况，与基于牛痘的载体相比，它们在免疫功能低下的个体中可能是更安全的免疫原，因为它们在没有有效复制的情况下在大多数哺乳动物细胞中表达转基因。
