Xing Yiping, Huang Zuhu, Lin Yan, Li Jun, Chou Te-Hui, Lu Shan, Wang Shixia
Department of Infectious Diseases, Nanjing Medical University, and China-US Vaccine Research Center, Jiangsu Province Hospital, Nanjing 210029, China.
Vaccine. 2008 Sep 19;26(40):5145-52. doi: 10.1016/j.vaccine.2008.03.072. Epub 2008 Apr 18.
Hepatitis B Virus (HBV) infection remains a major worldwide infectious disease with serious long-term morbidity and mortality. The limited selections of drug treatment are not able to control the progress of disease in people with active and persistent HBV infection. Immunotherapy to control the degree of viral infection is one possible alternative solution to this challenge. HBV DNA vaccines, with their strong ability to induce cell-mediated immune responses, offer an attractive option. HBV surface protein is important in viral immunity. Re-establishing anti-S immunity in chronic HBV infected patients will bring significant benefit to the patients. Previous studies have shown that HBV S DNA vaccines are immunogenic in a number of animal studies. In the current study, we further investigated the effect of glycosylation to the expression and immunogenicity of S DNA vaccines. Our results demonstrate that deglycosylation at the two potential N-linked glycosylation sites in S protein resulted in a significant decrease of S-specific cell-mediated immune responses, but did not affect anti-S antibody responses. This finding provides important direction to the development of S DNA vaccines to elicit the optimal and balanced antibody and cell-mediated immune responses to treat people with HBV chronic infections.
乙型肝炎病毒(HBV)感染仍然是一种主要的全球性传染病,会导致严重的长期发病和死亡。药物治疗选择有限,无法控制活动性和持续性HBV感染患者的疾病进展。免疫疗法以控制病毒感染程度是应对这一挑战的一种可能的替代解决方案。具有强大诱导细胞介导免疫反应能力的HBV DNA疫苗提供了一个有吸引力的选择。HBV表面蛋白在病毒免疫中很重要。在慢性HBV感染患者中重新建立抗-S免疫将给患者带来显著益处。先前的研究表明,HBV S DNA疫苗在多项动物研究中具有免疫原性。在本研究中,我们进一步研究了糖基化对S DNA疫苗表达和免疫原性的影响。我们的结果表明,S蛋白中两个潜在的N-连接糖基化位点去糖基化导致S特异性细胞介导免疫反应显著降低,但不影响抗-S抗体反应。这一发现为开发S DNA疫苗以引发最佳且平衡的抗体和细胞介导免疫反应来治疗HBV慢性感染患者提供了重要方向。