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

In order to design optimized DNA vectors as genetic vaccines against infect ions with the hepatitis B virus (HBV) we investigated if secretion or reten tion of the viral antigens has an influence on the quality and quantity of the humoral immune response. Intramuscular injection of plasmid DNA encodin g 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 secre tion-competent small S envelope protein elicited strong and sustained immun ity. 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 pr eS1- and preS2-specific antibodies, unless antigen secretion was blocked. A ccessibility of preS antigens to B-cells that can be achieved by generating extracellular forms of the envelope proteins is thus critical to elicit hu moral responses. Such DNA constructs carrying preS1 determinants are promis ing candidates for the development of multivalent HBV vaccines. (C) 1999 El sevier Science Ltd. All rights reserved.