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

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Abstract
B7 co‐stimulation is essential for activating resting T cells following antigen recognition by the T cell receptor. To determine whether B7 has adjuvant activities on human immunodeficiency virus type‐1 (HIV‐1)‐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‐inoculated with the DNA vaccine. The delayed‐type hypersensitivity response and cytotoxic T lymphocyte (CTL) activity were significantly enhanced when B7‐2 expression plasmid was co‐inoculated with the DNA vaccine, but were unaffected when the B7‐1 expression plasmid was used with the vaccine instead. The immunological response enhanced by B7‐2 decreased below the level of mice immunized with the DNA vaccine in combination with CTLA4Ig, an inhibitor of the B7/CD28 co‐stimulatory signal, suggesting that this signal is critical for the enhanced response induced by co‐inoculation of the DNA vaccine and B7‐2 expression plasmid. This enhancement appeared to occur via an interferon‐γ (IFN‐γ)‐dependent mechanism, as combined administration of the B7‐2 plasmid and neutralizing anti‐IFN‐γ antibody abrogated the virus‐specific cell‐mediated immunity. These results suggest that this gene‐based co‐inoculation strategy using HIV‐1 viral antigen and B7‐2 co‐stimulatory molecule could be a powerful means of combating HIV‐1 infection.