COSTIMULATORY PROTEIN B7-1 ENHANCES THE CYTOTOXIC T-CELL RESPONSE ANDANTIBODY-RESPONSE TO HEPATITIS-B SURFACE-ANTIGEN

There is a need for more effective therapy for chronic virus infection s, A principle natural mechanism for elimination of virus-infected hos t cells is activation of viral antigen-specific cytotoxic T lymphocyte s (CTL), In an effort to develop methods of inducing virus-specific CT L responses that might be utilized in therapy of virus infections, we have investigated the effect of B7, a costimulatory factor for T-cell activation, In this study we show that delivery of genes encoding huma n B7-1 and a viral antigen in the same recombinant viral vector to cel ls of mice induces a greater viral antigen-specific CTL response than does similar delivery of the viral antigen gene alone, Two recombinant adenovirus vectors were constructed with the foreign genes inserted i n the early region 3. One of them (Ad1312) directed expression of the surface antigen gene of hepatitis B virus (HBS); the other (Ad1310) di rected coexpression of HBS and human B7-1 (CD80) by means of an intern al ribosomal entry site placed between the two coding sequences, When inoculated into BALB/c mice, both vectors induced a viral surface anti gen-specific CTL response, The response induced by Ad1310 Ir as strong er than that by Ad1312 as measured by a chromium release assay for CTL activity and limiting dilution analysis for CTL precursor frequency, indicating that the B7-1 gene co-delivered with the HBS gene had an en hancing effect on the CTL response against surface antigen, Ad1310 als o induced a higher titer of antibody against surface antigen than did Ad1312. This result suggests that expression of a costimulatory protei n and a viral antigen in the same cells in vivo induces stronger immun e responses than expression of the antigen alone. This could be a nove l strategy for development of both preventive and therapeutic vaccines against infectious agents.