Yang S-H, Lee C-G, Park S-H, Im S-J, Kim Y-M, Son J-M, Wang J-S, Yoon S-K, Song M-K, Ambrozaitis A, Kharchenko N, Yun Y-D, Kim C-M, Kim C-Y, Lee S-H, Kim B-M, Kim W-B, Sung Y-C
Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea.
Gene Ther. 2006 Jul;13(14):1110-7. doi: 10.1038/sj.gt.3302751. Epub 2006 Mar 9.
Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-gamma secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4(+) memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.
尽管慢性乙型肝炎（CHB）化疗最近取得了进展，但治疗停止后尚未实现有效的病毒抑制。为了研究乙型肝炎病毒（HBV）特异性T细胞反应是否可诱导并有助于治疗停止后的病毒抑制，我们对12名接受拉米夫定（LAM）治疗的CHB携带者进行了一项概念验证研究，使用一种包含大多数HBV基因以及基因工程白细胞介素-12 DNA（IL-12N222L）的DNA疫苗。当进行体外和/或培养的干扰素-γ酶联免疫斑点（ELISPOT）检测时，在治疗结束时和随访期间观察到了可检测到的HBV特异性干扰素-γ分泌T细胞反应。这些1型T细胞反应，特别是CD4(+)记忆T细胞反应，在治疗后至少可维持40周，并与病毒学反应相关，但与丙氨酸转氨酶升高无关。此外，LAM治疗下的DNA疫苗似乎耐受性良好，在CHB携带者中显示出50%的病毒学反应率。因此，DNA疫苗与化疗的联合治疗可能是治愈CHB的新免疫治疗方法之一。
