IMMUNOMODULATORY EFFECTS OF A PLASMID EXPRESSING B7-2 ON HUMAN IMMUNODEFICIENCY VIRUS-1-SPECIFIC CELL-MEDIATED-IMMUNITY INDUCED BY A PLASMID ENCODING THE VIRAL-ANTIGEN

B7 co-stimulation is essential for activating resting T cells followin g antigen recognition by the T cell receptor. To determine whether B7 has adjuvant activities on human immunodeficiency virus type-1 (HIV-l) -specific immunity induced by inoculation of a plasmid encoding HIV-1 env and rev (DNA vaccine), B7-1 and B7-2 expression plasmids were co-i noculated with the DNA vaccine. The delayed-type hypersensitivity resp onse and cytotoxic T lymphocyte (CTL) activity were significantly enha nced when B7-2 expression plasmid was co-inoculated with the DNA vacci ne, but were unaffected when the B7-1 expression plasmid was used with the vaccine instead. The immunological response enhanced by B7-2 decr eased below the level of mice immunized with the DNA vaccine in combin ation with CTLA4Ig, an inhibitor of the B7/CD28 co-stimulatory signal, suggesting that this signal is critical for the enhanced response ind uced by coinoculation of the DNA vaccine and B7-2 expression plasmid. This enhancement appeared to occur via an interferon-gamma (IFN-gamma) -dependent mechanism, as combined administration of the B7-2 plasmid a nd neutralizing anti-IFN-gamma antibody abrogated the virus-specific c ell-mediated immunity. These results suggest that this gene-based co-i noculation strategy using HIV-I viral antigen and B7-2 costimulatory m olecule could be a powerful means of combating HIV-1 infection.