An Orally Delivered Booster Vaccine Candidate for Hepatitis B

描述（由申请人提供）：有3.5亿人慢性感染B型肝炎病毒，他们具有肝硬化和肝癌的高风险，每年导致约100万人死亡。这是一个惊人的速度，因为市场上已经有一种安全有效的疫苗超过20年。生产、分配和管理的高成本限制了这种疫苗在发展中国家的使用。诊所就诊的不便和对注射的恐惧限制了全世界的依从性。NIH的目标是开发新的疫苗和递送技术，以实现更完整的疫苗接种覆盖率。这项研究的长期目标是开发一种在环境温度下安全、有效和稳定的口服疫苗，并降低生产、分销和交付成本，同时提高合规性。该项目最初的重点是为高危人群和反应不良者提供B型肝炎加强治疗。 基于植物的生产系统有可能实现理想口服疫苗的目标。这些在动物试验中显示出巨大的希望，包括植物产生的B型肝炎抗原在人类临床试验中引发免疫应答的能力。然而，由于抗原的低表达和加工限制所施加的实际限制，该技术的发展受到限制。 在第一阶段，B型肝炎抗原水平增加了30倍以上，并建立了保留抗原完整性的处理方法。这种改进的材料在口服给小鼠时能够引起强烈的免疫反应。在第二阶段，研究重点是优化和表征可以商业化的最终产品。这包括1）高表达系的优化和表征，2）提供可口且稳定的产品形式的加工方法，以及3）小鼠中的免疫应答，使得其产生与注射疫苗相当的保护性应答。第二阶段目标的成功完成将导致临床试验和与人类健康合作伙伴的商业化道路。 公共卫生相关性：该项目与公共卫生的相关性在于，它可以导致廉价、稳定和有效的B型肝炎口服疫苗。这种疫苗可用于对现有疫苗反应不良的高危人群，以及由于成本限制而无法获得现有疫苗的发展中地区。这项研究也可能为以类似方式接种其他疫苗铺平道路。

DESCRIPTION (provided by applicant): There are 350 million people chronically infected with hepatitis B virus who have a high risk for cirrhosis of the liver and liver cancer resulting in approximately a million deaths annually. This is an alarming rate as there has been a safe and efficacious vaccine on the market for more than twenty years. High costs of production, distribution and administration have limited use of this vaccine in developing nations. The inconvenience of clinic visits and fear of injections restrict compliance worldwide. It is an NIH goal to develop new vaccines and delivery technologies that allow more complete vaccination coverage. The long-term objective of this research is to develop an oral vaccine that is safe, effective and stable at ambient temperatures, as well as reducing costs of production, distribution and delivery while boosting compliance. The initial focus of this project is for hepatitis B booster treatments for at-risk individuals and poor responders. Plant-based production systems have the potential to meet the goals of the ideal oral vaccine. These have shown great promise in animal trials including the ability of a plant-produced hepatitis B antigen to elicit an immune response in a human clinical trial. However, development of this technology has been limited because of the practical limitations imposed by low expression of the antigen and processing constraints. In Phase I, hepatitis B antigen levels were increased by more than 30-fold and processing methods were established that retained the antigen integrity. This improved material was able to elicit a robust immune response when orally fed to mice. In Phase II, the research is focused on optimizing and characterizing a final product that can be commercialized. This includes 1) optimization and characterization of a high expressing line, 2) a processing method that provides a palatable and stable form of the product, and 3) an immune response in mice so that it elicits a comparable protective response as that of the injected vaccine. Successful completion of Phase II aims will lead to a clinical trial and to a commercialization path with a human health partner. PUBLIC HEALTH RELEVANCE: The relevance of this project to public health is that it can lead to an inexpensive, stable, and effective oral vaccine for hepatitis B. Such a vaccine can be used for at-risk individuals who respond poorly to the current vaccine and in developing areas where the current vaccine is unavailable due to cost constraints. This research may also pave the way for other vaccines to be administered in a similar fashion.