Hu Jiafen, Schell Todd D, Peng Xuwen, Cladel Nancy M, Balogh Karla K, Christensen Neil D
Jake Gittlen Cancer Research Foundation, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
J Vaccines Vaccin. 2010 Aug 20;1(1). doi: 10.4172/2157-7560.1000101.
We have established an HLA-A2.1 transgenic rabbit /cottontail rabbit papillomavirus (CRPV) infection model. Using this novel transgenic animal model, we reported earlier that a multivalent epitope DNA vaccine (CRPVE1ep1-5) containing five HLA-A2.1 restricted epitopes from CRPVE1 (42-50, 149-157, 161-169, 245-253 and 303-311) was successful in providing strong and specific protective and therapeutic immunity. Among these five epitopes, two (161-169 and 303-311) have been proven to stimulate strong immunity in both HLA-A2.1 transgenic mouse and rabbit models. In the current study, we further identified the remaining three epitopes (CRPVE1/42-50,149-157, 245-253) in both animal models. CRPVE1/149-157 was able to induce specific CTL responses in HLA-A2.1 transgenic mice by DNA immunization but undetectable by peptide immunization. CRPVE1/42-50 and 245-253 failed to respond in HLA-A2.1 transgenic mice either by peptide or DNA immunization. All the three epitopes when administrated as DNA vaccines, however, were able to stimulate strong protective immunity in HLA-A2.1 transgenic rabbits in a dose dependent manner. Among the five epitopes, two (CRPVE1/ 303-311and CRPVE1/149-157) DNA vaccines also showed specific therapeutic effects in CRPV-infected HLA-A2.1 transgenic rabbits. Taken together, the HLA-A2.1 transgenic rabbit model recognized more epitopes than did the HLA-A2.1 transgenic mouse model. Our data demonstrate that the HLA-A2.1 transgenic rabbit model can complement the HLA-A2.1 transgenic mouse model for the development and testing of new HLA-A2.1 restricted prophylactic and therapeutic T cell based DNA vaccines.
我们建立了一种HLA - A2.1转基因兔/棉尾兔乳头瘤病毒（CRPV）感染模型。利用这个新型转基因动物模型，我们之前报道过一种包含来自CRPV E1的五个HLA - A2.1限制性表位（42 - 50、149 - 157、161 - 169、245 - 253和303 - 311）的多价表位DNA疫苗（CRPVE1ep1 - 5）成功提供了强大且特异性的保护性和治疗性免疫。在这五个表位中，有两个（161 - 169和303 - 311）已被证明在HLA - A2.1转基因小鼠和兔模型中均能刺激产生强大的免疫反应。在当前研究中，我们在两种动物模型中进一步鉴定了其余三个表位（CRPVE1/42 - 50、149 - 157、245 - 253）。CRPVE1/149 - 157通过DNA免疫能够在HLA - A2.1转基因小鼠中诱导特异性CTL反应，但肽免疫检测不到。CRPVE1/42 - 50和245 - 253无论是通过肽免疫还是DNA免疫在HLA - A2.1转基因小鼠中均无反应。然而，当将所有这三个表位作为DNA疫苗给药时，它们能够以剂量依赖性方式在HLA - A2.1转基因兔中刺激产生强大的保护性免疫。在这五个表位中，两种（CRPVE1/303 - 311和CRPVE1/149 - 157）DNA疫苗在感染CRPV的HLA - A2.1转基因兔中也显示出特异性治疗效果。综上所述，HLA - A2.1转基因兔模型比HLA - A2.1转基因小鼠模型识别更多的表位。我们的数据表明，HLA - A2.1转基因兔模型可以补充HLA - A2.1转基因小鼠模型，用于开发和测试新的基于HLA - A2.1限制性预防性和治疗性T细胞的DNA疫苗。
