CHARACTERIZATION OF HUMORAL AND CD4(-RESPONSES AFTER GENETIC IMMUNIZATION WITH RETROVIRAL VECTORS EXPRESSING DIFFERENT FORMS OF THE HEPATITIS-B VIRUS CORE AND E-ANTIGENS() CELLULAR)

The humoral and CD4(+) cellular immune responses in mice following gen etic immunization with three retroviral vectors encoding different for ms of hepatitis B virus core antigen (HBcAg) and e antigen (HBeAg) wer e analyzed, The retroviral vectors induced expression of intracellular HBcAg (HBc[3A4]), secreted HBeAg (HEe[5A2]), or an intracellular HBcA g-neomycin phosphoryltransferase fusion protein (HBc-NEO[6A3]), Specif ic antibody levels and immunoglobulin G isotype restriction were highl y dependent on both the host major histocompatibility complex and the transferred gene, Humoral and CD4(+) cellular HBcAg and/or HBeAg (HBc/ eAg)-specific immune responses following retroviral vector immunizatio n were of a lower magnitude but followed the same characteristics comp ared with those after immunization with HBc/eAg in adjuvant, Two facto rs influenced the humoral responses, First, in vivo depletion of CD8() cells in HBc-NEO [6A3]-immunized H-2(k) mice abrogated both HBcAg-sp ecific antibodies and in vitro-detectable cytotoxic T lymphocytes. Sec ond, priming of H-2(b) mice with an HBc/eAg-derived T-helper (Th) pept ide in adjuvant prior to retroviral vector immunization greatly enhanc ed the HBc/eAg-specific humoral responses to all three vectors, sugges ting that insufficient HBc/eAg-specific CD4(+) Th-cell priming limits the humoral responses, In conclusion, direct injection of retroviral v ectors seems to be effective in priming HBc/eAg-specific CD8(+) but co mparatively inefficient in priming CD4(+) Th cells and subsequently sp ecific antibodies, However, the limited HBc/eAg-specific CD4(+) cell p riming can effectively be circumvented by prior administration of a re combinant or synthetic form of HBc/eAg in adjuvant.