Macrophage inflammatory protein-1 alpha (MIP-1 alpha) expression plasmid enhances DNA vaccine-induced immune response against HIV-1

CD8(+) cell-secreted CC-chemokines, MIP-1 alpha, and MIP-beta have recently been identified as factors which suppress HIV. In this study we co-inocula ted MIP-1 alpha expression plasmid with a DNA vaccine constructed from HIV- 1 pCMV160IIIB and pcREV, and evaluated the effect of the adjuvant on HIV-sp ecific immune responses following intramuscular and intranasal immunization . The levels of both cytotoxic T lymphocyte (CTL) activity and DTH showed t hat HIV-specific cell-mediated immunity (CMI) was significantly enhanced by co-inoculation of the MIP-1 alpha expression plasmid with the DNA vaccine compared with inoculation of the DNA vaccine alone. The HIV-specific serum IgG1/IgG2a ratio was significantly lowered when the plasmid was co-inoculat ed in both intramuscular and intranasal routes, suggesting a strong elicita tion of the T helper (Th) 1-type response. When the MIP-1 alpha expression plasmid was inoculated intramuscularly with the DNA vaccine, an infiltratio n of mononuclear cells was observed at the injection site. After intranasal administration, the level of mucosal secretory IgA antibody was markedly e nhanced. These findings demonstrate that MIP-1 alpha expression plasmid ino culated together with DNA vaccine acts as a strong adjuvant for eliciting T h1-derived immunity.