Oral hepatitis B vaccine candidates produced and delivered in plant material.

Hepatitis B is a major global health problem; approximately two billion people are infected with the virus worldwide, despite the fact that safe and efficacious vaccines have been developed and used for nearly 20 years. Prohibitive costs for vaccine purchase and administration restrict uptake in many developing nations. Agencies such as the Global Alliance for Vaccination and Immunization are helping to make current vaccines more available, but reduced costs would greatly aid this effort. Oral delivery is an option to reduce the expense of administering hepatitis B vaccines. It may also improve compliance, and orally delivered vaccines may be more efficacious among poor responders to current vaccines. However, to induce protective efficacy, oral administration may require encapsulation of antigen and delivery of large doses. Plant-based expression systems offer an oral delivery alternative with low production costs, and they also encapsulate the antigen. Some plant-based systems also stabilize antigen and therefore reduce storage and distribution costs. The hepatitis B major surface antigen has been expressed in several plant systems. A variety of regulatory sequences and subcellular targets have been used to achieve expression suitable for early stage clinical trials. However, further increase in expression will be necessary for practical and efficacious products. Appropriate processing can yield palatable products with uniform antigen concentration. The antigen expressed in plant systems shows extensive disulphide cross-linking and oligomerization and forms virus-like particles. Oral delivery of the antigen in plant material can induce a serum antibody response, prime the immune system for a subsequent injection of antigen and give a boosted response to a prior injection. Small scale clinical trials in which the antigen has been delivered orally in edible plant material indicate safety and immunogenicity.