Woo P C, Wong L P, Zheng B J, Yuen K Y
Department of Microbiology, University Pathology Building, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong.
Vaccine. 2001 Apr 6;19(20-22):2945-54. doi: 10.1016/s0264-410x(00)00530-2.
A novel vaccine for hepatitis B virus (HBV) was designed by putting a naked DNA vaccine carrying hepatitis B surface antigen (HBsAg) into live-attenuated Salmonella typhimurium. Mucosal immunization by the oral route in mice showed significantly stronger cytotoxic T lymphocyte (CTL) response than recombinant HBsAg vaccination (P < 0.01 at an effector:target ratio of 100:1), while comparable to intramuscular naked DNA immunization at all effector:target ratios. Contrary to previous reports on naked DNA vaccines given intramuscularly, the IgG antibody response induced by the mucosal DNA vaccine is relatively weak when compared to recombinant HBsAg vaccine (P < 0.001 at day 21). These findings are supported by a high interferon-gamma but a low interleukin-4 level detected in the supernatant of splenic cell cultures obtained from mucosally immunized mice. As distinct to recombinant HBsAg vaccine which is effective for protection, oral mucosal DNA vaccine should be considered as a candidate for therapeutic immunization in chronic HBV infection, donor immunization before adoptive transfer of HBV-specific CTL to HBsAg positive bone marrow transplant recipients, and immunization of non-responders to recombinant HBsAg vaccine. This strongly cellular and relatively absent humoral response may make this vaccine a better candidate as a therapeutic vaccine for chronic HBV carriers than naked DNA vaccines, as the humoral response is relatively less important for the clearance of HBV from hepatocytes, but its presence may lead to side effects such as serum sickness and immune complex deposition in chronic HBV carriers.
通过将携带乙肝表面抗原（HBsAg）的裸DNA疫苗导入减毒活鼠伤寒沙门氏菌中，设计出了一种新型乙肝病毒（HBV）疫苗。小鼠口服途径的黏膜免疫显示，其细胞毒性T淋巴细胞（CTL）反应明显强于重组HBsAg疫苗（效应细胞：靶细胞比例为100:1时，P < 0.01），而在所有效应细胞：靶细胞比例下，与肌肉注射裸DNA免疫相当。与先前关于肌肉注射裸DNA疫苗的报道相反，黏膜DNA疫苗诱导的IgG抗体反应与重组HBsAg疫苗相比相对较弱（第21天时，P < 0.001）。这些发现得到了从黏膜免疫小鼠脾脏细胞培养上清液中检测到的高干扰素-γ水平和低白细胞介素-4水平的支持。与有效提供保护的重组HBsAg疫苗不同，口服黏膜DNA疫苗应被视为慢性HBV感染治疗性免疫、将HBV特异性CTL过继转移给HBsAg阳性骨髓移植受者之前供体免疫以及重组HBsAg疫苗无反应者免疫的候选疫苗。这种强烈的细胞反应和相对缺乏的体液反应可能使这种疫苗比裸DNA疫苗更适合作为慢性HBV携带者的治疗性疫苗，因为体液反应对于从肝细胞中清除HBV相对不那么重要，但其存在可能导致慢性HBV携带者出现血清病和免疫复合物沉积等副作用。
