人IFNα-2b对HPV11-E7 DNA疫苗的免疫佐剂效应

Role of human interferon α-2b as an immunological adjuvant for human papillomavirus （HFV）11-E7 DNA vaccine

目的探讨人IFNα-2b对HPV11-E7DNA疫苗的免疫佐剂效应。方法将28只BALB／c小鼠随机分为4组，每组7只。融合基因组pcDNA3．1（＋）-IFNα-2b—HPV11-E7组，分别肌内注射。初次免疫后2周以同样方法和相同剂量加强免疫，2次免疫后再以同样方法和相同剂量加强免疫。于6周后剖杀BALB／c小鼠，取脾并分离脾淋巴细胞，进行细胞培养并刺激单个核细胞产生细胞因子，用流式细胞仪检测Th1、Th2细胞因子比例。结果融合基因组pcDNA3．1（＋）-IFNα-2b—HPV11-E7组的IFN-γ水平明显高于pcDNA3．1（＋）-HPV11-E7组，差异具有统计学意义（P〈0．001）；融合基因组与pcDNA3．1（＋）-HPV11-E7组的IFN-γ水平明显高于对照组PBS组及空载质粒pcDNA3．1（＋）组，差异有统计学意义（P〈0．001）；两对照组之间的IFN-γ水平差异无统计学意义（P〉0．05）。各组之间的IL-4及IL-10水平差异无统计学意义（P〉0．05）。结论人IFNα-2b能明显加强HPV11-E7的免疫原性，提高免疫小鼠的T淋巴细胞免疫能力，IFNα-2b以增强Th1型应答为主，对Th2型应答无明显影响。

Objective To investigate the role of human interferon （IFN）α-2b in cellular and humoral immune response in BALB/c mice. Methods Plasmids pcDNA3.1 （＋）-HPVll-E7 and peDNA3.1 （＋）- IFNα-2b-linker-HPV11-E7 were constructed. Twenty-eight BALB/c mice were randomly and equally divided into four groups to be immunized with pcDNA3.1 （＋）-IFNα-2b-linker-HPV11-E7 （group D）, pcDNA3.1 （＋） -HPV11-E7 （group C）, pcDNA3.1 （＋）（group B ）, phosphate buffered solution （group A）, respectively, by intramuscular injection. Repetitive immunization was carried out on week 2 and 4. On week 6, mice were killed, splenocytes were isolated, cultured, and stimulated followed by the detection of expression level of IFN-% interleukin （IL）-4 and -10 in CD3^＋ cells and CD4^＋ cells. Results The level of IFN-γ （expressed as the absorbance at 460 nm） in group C was significantly higher than that in groups A and B （4.36 ± 0.42 vs 3.20 ± 0.41 and 3.29 ± 0.35, both P 〈 0.001 ）, but lower than that in group D （4.36 ± 0.42 vs 6.39 ± 0.05, P 〈 0.001 ）, and there was no significant difference between group A and B （P 〉 0.05）. No significant difference was noted in the levels of IL-4 or IL-10 among these 4 groups （P 〉 0.05）. Conclusions IFNα-2b can enhance the immunogenicity of HPV11-E7 and strengthen cellular immunity, especially Thl-type immune response to HPV11-E7 DNA vaccine in mice.