DNA-mediated immunization to hepatitis B virus envelope proteins: preS antigen secretion enhances the humoral...

In order to design optimized DNA vectors as genetic vaccines against infections with the hepatitis B virus (HBV) we investigated if secretion or retention of the viral antigens has an influence on the quality and quantity of the humoral immune response. Intramuscular injection of plasmid DNA encoding the HBV large L envelope protein, known to be retained within host cells, induced only a weak response in mice whereas a vector expressing the secretion-competent small S envelope protein elicited strong and sustained immunity. Immunization with rearranged envelope genes further demonstrated that secretion affects the magnitude of the immune response. In situ expression of modified small and middle envelope genes carrying C-terminally attached epitopes are derived from the preS1 region of L generated high titers of preS1- and preS2-specific antibodies, unless antigen secretion was blocked. Accessibility of preS antigens to B-cells that can be achieved by generating extracellular forms of the envelope proteins is thus critical to elicit humoral responses. Such DNA constructs carrying preS1 determinants are promising candidates for the development of multivalent HBV vaccines.