HIV-1-SPECIFIC CELL-MEDIATED-IMMUNITY IS ENHANCED BY CO-INOCULATION OF TCA3 EXPRESSION PLASMID WITH DNA VACCINE

We developed a candidate DNA vaccine designated pCMV160IIIB with pcREV (pCMV160IIIB/REV) that encodes gp160 of human immunodeficiency virus (HIV)-1(IIIB) and Rev driven by the cytomegalovirus (CMV) promotor. Th is vaccine induced both HIV-1-specific antibodies and cytotoxic T lymp hocyte (CTL) activity. In the present study, we inoculated the TCA3 ex pression plasmid into mouse skeletal muscle with pCMV160IIIB/REV to de termine whether this cytokine expression plasmid was able to modify th e immune response. Results of a delayed-type hypersensitivity (DTH) as say using footpad swelling as well as those of a CTL assay clearly dem onstrated that cell-mediated immunity (CMI) elicited by co-inoculation of pCMV160IIIB/REV with the TCA3 expression plasmid was markedly enha nced compared with that obtained using pCMV160IIIB/REV alone. When TCA 3 expression plasmid was inoculated with anti-TCA3 antibody, enhanceme nt of the DTH response was suppressed below the level of that obtained with pCMV160IIIB/REV alone. The titre of HIV-1-specific IgG2a was sli ghtly high when pCMV160IIIB/REV was co-inoculated with this plasmid, s uggesting that T-helper 1 (Th1) response was predominant in TCA3-inocu lated mice. Infiltration of mononuclear cells was seen in the muscles at sites where TCA3 expression plasmid had been inoculated. Our presen t data suggest that TCA3 expression plasmid has potent adjuvant activi ty that results in an augmented CMI response.