A QUALITATIVE PROGRESSION IN HIV TYPE-1 GLYCOPROTEIN-120-SPECIFIC CYTOTOXIC CELLULAR AND HUMORAL IMMUNE-RESPONSES IN MICE RECEIVING A DNA-BASED GLYCOPROTEIN-120 VACCINE

The potential for eliciting humoral and cytotoxic T lymphocyte (CTL) r esponses to HIV-1 gp120 by gene gun-based DNA immunization in mice was examined. We speculated that the induction of de novo antigen product ion in the epidermis of BALB/c mice following particle bombardment-bas ed gene delivery would result in both MHC class I- and class II-mediat ed antigen presentation for the elicitation of CTL and antibody respon ses, respectively. Following epidermal delivery of microgram quantitie s of an expression plasmid, gp120 production resulted in the appearanc e of MHC class I-restricted, CD8(+) CTL responses. gp120-specific CTL responses peaked following a booster immunization, then declined with the appearance of gp120-specific IgG responses when additional booster immunizations were administered. This qualitative progression in the nature of gp120-specific immune responses with subsequent immunization s was paralleled by a simultaneous shift in the interferon-gamma and i nterleukin 4 release profiles following antigen stimulation of splenoc ytes in vitro. The simultaneous shifts in immune responses and cytokin e release profiles indicate that the progression of antigen-specific C TL and IgG responses in gp120 DNA-immunized mice may be mediated throu gh changes in the in vivo production of cytokines, such as those assoc iated with the Th1 and Th2 subsets of CD4(+) cells.