Department of Infectious Diseases, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Vaccine. 2010 Oct 21;28(45):7288-96. doi: 10.1016/j.vaccine.2010.08.081. Epub 2010 Sep 8.
Gene-based hepatitis B virus (HBV) vaccines have been proposed as a novel approach to improve the immunogenicity toward non-responders and to allow for protection against potential viral escape mutants. Furthermore, there is significant interest in using DNA or viral vector vaccines to serve as therapeutic agents to treat chronic HBV infections that are resistant to existing drug therapies. However, the key protective antigen of HBV, the surface protein (HBsAg), can be expressed in three different sizes due to its multiple translational initiation sites: small, middle, and large forms of HBsAg. It is not clear whether the immunogenicity of these HBsAg is same, especially their ability to elicit HBsAg-specific B cell and T cell immune responses in addition to the traditional serum HBsAg-specific antibody responses. In the current study, the immunogenicity of three forms of HBsAg DNA vaccines was analyzed individually in a mouse model. Our results indicated that different forms of the HBsAg have unique immunogenicity profiles and this information is useful for the selection of optimal gene-based HBV vaccines for further improved prophylactic and therapeutic applications.
基因乙型肝炎病毒 (HBV) 疫苗被提议作为一种新方法,以提高对无应答者的免疫原性,并允许对潜在的病毒逃逸突变体进行保护。此外,人们对使用 DNA 或病毒载体疫苗作为治疗剂来治疗对现有药物治疗有抗药性的慢性 HBV 感染产生了浓厚的兴趣。然而,HBV 的关键保护性抗原,表面蛋白 (HBsAg),由于其多个翻译起始位点,可以表达为三种不同的大小:小、中、大形式的 HBsAg。目前尚不清楚这些 HBsAg 的免疫原性是否相同,特别是它们在引发 HBsAg 特异性 B 细胞和 T 细胞免疫反应的能力,除了传统的血清 HBsAg 特异性抗体反应之外。在当前的研究中,在小鼠模型中单独分析了三种形式的 HBsAg DNA 疫苗的免疫原性。我们的结果表明,HBsAg 的不同形式具有独特的免疫原性特征,这些信息对于选择最佳的基因乙型肝炎病毒疫苗用于进一步改进预防性和治疗性应用是有用的。