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

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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-IMM-N (12))
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Koshy, Rajen
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Applied Biotechnology Institute
San Luis Obispo
United States
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Hayden, Celine A; Fischer, Maria E; Andrews, Bryan L et al. (2015) Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses. Vaccine 33:2881-6
Shah, Shweta; Hayden, Celine A; Fischer, Maria E et al. (2015) Biochemical and biophysical characterization of maize-derived HBsAg for the development of an oral vaccine. Arch Biochem Biophys 588:41-9
Hayden, Celine A; Smith, Emily M; Turner, Debra D et al. (2014) Supercritical fluid extraction provides an enhancement to the immune response for orally-delivered hepatitis B surface antigen. Vaccine 32:1240-6
Hayden, Celine A; Streatfield, Stephen J; Lamphear, Barry J et al. (2012) Bioencapsulation of the hepatitis B surface antigen and its use as an effective oral immunogen. Vaccine 30:2937-42
Hayden, Celine A; Egelkrout, Erin M; Moscoso, Alessa M et al. (2012) Production of highly concentrated, heat-stable hepatitis B surface antigen in maize. Plant Biotechnol J 10:979-84