Oral immunization with hepatitis B surface antigen expressed in transgenicplants

Oral immunogenicity of recombinant hepatitis B surface antigen (HBsAg) deri ved from yeast (purified product) or in transgenic potatoes (uncooked unpro cessed sample) was compared. An oral adjuvant, cholera toxin, was used to i ncrease immune responses. Transgenic plant material containing HBsAg was th e superior means of both inducing a primary immune response and priming the mice to respond to a subsequent parenteral injection of HBsAg. Electron mi croscopy of transgenic plant samples revealed evidence that the HBsAg accum ulated intracellularly; we conclude that natural bioencapsulation of the an tigen may provide protection from degradation in the digestive tract until plant cell degradation occurs near an immune effector site in the gut. The correlate of protection from hepatitis B virus infection is serum antibody titers induced by vaccination; the protective level in humans is 10 milliun its/ml or greater. Mice fed HBsAg-transgenic potatoes produced HBsAg-specif ic serum antibodies that exceeded the protective level and, on parenteral b oosting, generated a strong longlasting secondary antibody response. We hav e also shown the effectiveness of oral delivery by using a parenteral prime -oral boost immunization schedule. The demonstrated success of oral immuniz ation for hepatitis B virus with an "edible vaccine" provides a strategy fo r contributing a means to achieve global immunization for hepatitis B preve ntion and eradication.