Potentiating a DNA vaccine for HBV with electroporation

描述（由申请人提供）：急性B型肝炎病毒（HBV）感染通常是自限性的。 然而，长期感染的患者有患慢性肝脏炎症、肝硬化和肝癌的风险;而且，他们是其他人的主要污染源。 这些患者中只有少数通过抗病毒治疗治愈。 需要对这些患者进行治疗性疫苗接种。 慢性HBV感染与对病毒抗原的免疫应答性差相关。 这种免疫耐受不是由于突变病毒的出现或效应T细胞的消失。 相反，对HBV的免疫反应是错误的和低效的。 建立针对HBV的强免疫应答有助于诱导缓解甚至治愈疾病。 强烈的T细胞反应对于清除病毒至关重要。 DNA疫苗有效地诱导T细胞免疫。 电穿孔通过提供一致的、可重复的、高水平的免疫原表达，并诱导强烈的、高强度的免疫应答，正在成为DNA疫苗递送的选择方法。 在这些研究中，将在正常小鼠中测试基于电穿孔的针对HBV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。 匹配预定义标准的方案将在慢性HBV感染动物模型的II期中进行测试。

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.