An Orally Delivered Hepatitis B Vaccine

DESCRIPTION (provided by applicant): Hepatitis B is a major global health problem. About 350 million chronically infected people are at high risk for cirrhosis of the liver and liver cancer, resulting in appoximately a million deaths annually. Current va ccines command a 1 billion annual market. However, high costs of production, distribution and administration for these parenterally delivered vaccines limit their use in developing nations. Also, inconvenience of clinic visits and fear of injections restr ict compliance in developed nations. The long-term objective of this research is to develop an oral vaccine that is effective and stable at ambient temperatures, reducing costs of production, distribution and delivery, and boosting compliance. Maize has be en used in our lab to express antigens in stable formulations for viral and bacterial diseases that were orally delivered in large farm animal trials and human clinical trials. Vaccine candidates were well-tolerated, elicited humoral and mucosal immune res ponses and where tested conferred protection. Responses observed at secondary mucosal sites, indicate the applicability of these vaccines for sexually transmitted diseases. They can also induce a lactogenic response, implying potential for passive immunity . This research targets hepatitis B booster treatments for at risk individuals and poor responders, but may also be suitable for primary immunizations. The technology should be applicable to other diseases as well. Preliminary research with hepatitis B va ccines candidates has demonstrated expression in maize and the ability to elicit an antibody response in mice. This research has four aims. Firstly, to express a 1 mg dose of vaccine immunogen in an easily administered 10 g amount of grain material. This i s an order of magnitude more concentrated than reported with other plant systems. Levels at one third the target have already been achieved. Strategies to increase expression include introgression into germplasm suited to protein accumulation, increasing gene dosage, and developing new transgenic lines incorporating an improved seed promoter, a multicopy expression unit and alternative signals for subcellular targeting. The second aim is to evaluate the potential for an adjuvant to increase the efficiency of the immune response. The third aim is to identify a processing method to yield a palatable product without degrading the antigen. The fourth aim is to demonstrate safety, and humoral and mucosal immunogenicity of the product as an oral booster in mice. Completion of phase I aims will lead to a phase II proposal for a clinical trial. This will allow the product to enter a commercialization path with a human health partner. PUBLIC HEALTH RELEVANCE - PROJECT NARRATIVE: The relevance of this project to public health is that it can lead to a stable, inexpensive and orally delivered vaccine for hepatitis B. Such a vaccine can be used for at-risk individuals and in developing areas where the current vaccine is unavailable. This research may also pave th e way for other vaccines to be administered in a similar fashion.