Potentiating a DNA vaccine for HBV with electroporation

描述(申请人提供)：急性乙肝病毒(乙肝)感染通常是自限性的。然而，仍然长期感染的患者有患慢性肝炎、肝硬变和肝癌的风险；他们也是其他人的主要污染源。这些患者中只有一小部分人可以通过抗病毒治疗治愈。 这类患者需要进行治疗性疫苗接种。慢性乙肝病毒感染与病毒抗原免疫反应差有关。这种免疫耐受不是由于突变病毒的出现或效应器T细胞的消失。相反，对乙肝病毒的免疫反应是错误的和低效的。建立对乙肝病毒的强大免疫反应有助于诱导病情缓解，甚至治愈疾病。 强烈的T细胞反应对于清除病毒是必不可少的。DNA疫苗能有效地诱导T细胞免疫。电穿孔通过提供一致的、可重复性的、高水平的免疫原表达，并诱导强有力的、高强度的免疫反应，正在成为DNA疫苗交付的一种选择方法。在这些研究中，将在正常小鼠身上测试基于电穿孔的针对乙肝病毒的DNA免疫的治疗潜力。终点将包括反应的速度、幅度、持续时间、多特异性、多克隆性和分布。与预定标准匹配的方案将在第二阶段在慢性乙肝病毒感染的动物模型中进行测试。

DESCRIPTION (provided by applicant): Acute hepatitis B virus (HBV) infection is generally self-limited. However, patients remaining chronically infected are at risk for chronic liver inflammation, cirrhosis and liver carcinoma; also, they are a major source of contamination to others. Only a minority of these patients is cured by antiviral therapy. Therapeutic vaccination is needed for such patients. Chronic HBV infection correlates with poor immune responsiveness to viral antigens. Such immune tolerance is not due to emergence of mutant viruses or disappearance of effector T cells. Rather, immune response to HBV is misdirected and inefficient. Establishing a strong immune response to HBV could help to induce remission even cure the disease. Strong T cell responses are essential to clear the virus. DNA vaccines efficiently induce T cell immunity. Electroporation is becoming a method of choice for DNA vaccine delivery, by providing consistent, reproducible, high level, immunogen expression, and inducing vigorous, high magnitude immune responses. In these studies, therapeutic potential of electroporation-based DNA immunization against HBV will be tested in normal mice. End points will include rapidity, magnitude, duration, multispecificity, polyclonality and distribution of the response. Protocols matching predefined criteria will be tested in Phase II in animal models of chronic HBV infection.