Immunology/Immunotherapy Program, MCG Cancer Center, Georgia Health Science University, Augusta, GA, United States.
Vaccine. 2011 May 17;29(22):3909-16. doi: 10.1016/j.vaccine.2011.03.025. Epub 2011 Mar 21.
Even though hepatitis B virus(HBV) vaccines effectively prevent new cases of HBV infection, with approximately 350 million patients worldwide, chronic HBV infection remains a major health problem because of the associated complications (such as liver cirrhosis and hepatocellular carcinoma) and the limited treatment options. Immunotherapy has the potential to effectively control HBV replication. In this current study, we found that recombinant lentivectors could induce potent HBV surface antigen (HBsAg) specific T cell responses and humoral immune responses. Tagging the HBsAg with immunoglobulin Fc fragment further substantially increased the HBsAg specific immune responses. Remarkably, the HBS-Fc-lv lentivector could effectively break immune tolerance and induce potent HBsAg specific adaptive immune responses in HBsAg transgenic (Tg) mice with low serum level of HBsAg. More importantly, the induction of HBsAg specific immune responses in Tg mice accompanied seroconversion from HBsAg to anti-HBsAg antibody (anti-HBsAb). Our study demonstrated the potential of utilizing lentivector to treat chronic HBV infection following reduction of viral load with antiviral drug therapy.
尽管乙型肝炎病毒 (HBV) 疫苗可有效预防新的 HBV 感染,但由于相关并发症(如肝硬化和肝细胞癌)以及治疗选择有限,全球仍有约 3.5 亿慢性 HBV 感染者。免疫疗法具有有效控制 HBV 复制的潜力。在本研究中,我们发现重组慢病毒载体可诱导强烈的 HBV 表面抗原 (HBsAg) 特异性 T 细胞反应和体液免疫反应。将 HBsAg 与免疫球蛋白 Fc 片段结合可进一步显著提高 HBsAg 特异性免疫反应。值得注意的是,HBs-Fc-lv 慢病毒载体可有效打破免疫耐受,在 HBsAg 转基因 (Tg) 小鼠中诱导强烈的 HBsAg 特异性适应性免疫反应,而这些 Tg 小鼠的 HBsAg 血清水平较低。更重要的是,在 Tg 小鼠中诱导的 HBsAg 特异性免疫反应伴随着 HBsAg 向抗 HBsAg 抗体 (抗-HBsAb) 的血清转换。我们的研究表明,在抗病毒药物治疗降低病毒载量后,利用慢病毒载体治疗慢性 HBV 感染具有潜力。