DNA VECTOR CONSTRUCTS THAT PRIME HEPATITIS-B SURFACE ANTIGEN-SPECIFICCYTOTOXIC T-LYMPHOCYTE AND ANTIBODY-RESPONSES IN MICE AFTER INTRAMUSCULAR INJECTION

We tested the efficiency of induction of immune responses to the small hepatitis B surface antigen (HBsAg) in mice by intramuscular DNA immu nization using different vector constructs that allow high levels of H BsAg expression in mouse cells. The HBsAg-specific responses of class I-restricted cytotoxic T lymphocytes (CTL) and of B cells (serum antib ody titers) were measured. Following the intramuscular inoculation of 'naked' DNA, five different vector constructs of 4-8 kb, that containe d or did not contain an intron and/or the neo gene, in which HBsAg exp ression was driven by promoter sequences derived from the immediate ea rly region of HCMV, the SV40 enhancer/promoter region, or a retroviral 3' LTR efficiently primed responses of class I-restricted CD8(+) CTL precursors. In contrast, the constructs in which HBsAg expression was driven by HCMV-derived promoter sequences stimulated significantly hig her levels of HBsAg-specific serum antibody titers after intramuscular DNA injection than the SV40 or MPSV vector constructs. Large (15 kb) episomal vector constructs did not stimulate CTL or antibody responses , The data demonstrate that: (i) intramuscular DNA immunization repres ents an efficient technique for priming CTL and antibody responses to HBsAg; (ii) many vectors can be constructed that express an immunogeni c product after intramuscular inoculation of 'naked' DNA; (iii) the ef ficiency of the tested vector constructs to prime after DNA immunizati on, either a CTL response, or an antibody response, differs.