Furukawa Shinya, Akbar S M Fazle, Hasebe Aki, Horiike Norio, Onji Morikazu
Third Department of Internal Medicine, Ehime University, School of Medicine, Shigenobu-Cho, Onsen-Gun, Ehime 791-0295, Japan.
Immunobiology. 2004;209(7):551-7. doi: 10.1016/j.imbio.2004.07.001.
Vaccines containing hepatitis B surface antigen (HBsAg) induce antibody to HBsAg (anti-HBs) in most normal individuals and protects them from hepatitis B virus (HBV) infection. However, these vaccines are not efficient at inducing anti-HBs in immunosuppressed individuals, especially in immunosuppressed HBV carriers. The aim of this study was to prepare and to assess the efficacy of a dendritic cell (DC)-based vaccine in an immunosuppressed HBV transgenic mouse (HBV-Tg), an animal model of the HBV carrier state. In order to prepare immunosuppressed HBV-Tg, HBV-Tg were injected with FK-506, an immunosuppressive agent, once daily, intraperitoneally for 15 days. Spleen cells of immunosuppressed HBV-Tg expressed very little mRNAs for interleukin-2 and interferon-gamma. DCs were isolated from the spleen of immunosuppressed HBV-Tg and cultured with HBsAg (100 microg) for 48 h to prepare HBsAg-pulsed DCs. Immunosuppressed HBV-Tg expressing HBsAg in the sera were administered with HBsAg-pulsed DCs or unpulsed DCs or HBsAg in adjuvant for different durations. Immunosuppressed HBV-Tg (n = 8) twice administered with HBsAg-pulsed DCs expressed anti-HBs in the sera within 6 weeks of first injection. Seven of eight immunosuppressed HBV-Tg remained positive for anti-HBs in the sera for the next 12 weeks of observation in spite of receiving daily injection of FK-506 for the entire duration. However, immunosuppressed HBV-Tg administered with unpulsed DCs or HBsAg in adjuvant did not express anti-HBs in the sera. The data show that DCs from immunosuppressed HBV-Tg can be loaded with HBsAg to prepare immunogenic HBsAg-pulsed DCs. HBsAg-pulsed DCs induced anti-HBs in immunosuppressed HBV-Tg. This approach may be of use to induce and maintain anti-HBs in immunosuppressed human HBV carriers.
含有乙肝表面抗原（HBsAg）的疫苗可在大多数正常个体中诱导产生抗HBsAg抗体（抗-HBs），并保护他们免受乙肝病毒（HBV）感染。然而，这些疫苗在免疫抑制个体中诱导产生抗-HBs的效率不高，尤其是在免疫抑制的HBV携带者中。本研究的目的是制备并评估一种基于树突状细胞（DC）的疫苗在免疫抑制的HBV转基因小鼠（HBV-Tg）（一种HBV携带状态的动物模型）中的疗效。为了制备免疫抑制的HBV-Tg，每天一次腹腔注射免疫抑制剂FK-506，持续15天。免疫抑制的HBV-Tg的脾细胞中白细胞介素-2和干扰素-γ的mRNA表达非常少。从免疫抑制的HBV-Tg的脾脏中分离出DC，并与HBsAg（100微克）一起培养48小时，以制备HBsAg脉冲DC。将血清中表达HBsAg的免疫抑制HBV-Tg在不同时间段内给予HBsAg脉冲DC或未脉冲DC或佐剂中的HBsAg。首次注射后6周内，两次给予HBsAg脉冲DC的免疫抑制HBV-Tg（n = 8）血清中表达了抗-HBs。在接下来12周的观察期内，尽管在整个期间每天都注射FK-506，但8只免疫抑制HBV-Tg中有7只血清中的抗-HBs仍保持阳性。然而，给予未脉冲DC或佐剂中HBsAg的免疫抑制HBV-Tg血清中未表达抗-HBs。数据表明，免疫抑制的HBV-Tg的DC可以负载HBsAg以制备具有免疫原性的HBsAg脉冲DC。HBsAg脉冲DC在免疫抑制的HBV-Tg中诱导产生了抗-HBs。这种方法可能有助于在免疫抑制的人类HBV携带者中诱导并维持抗-HBs。
