HIV-specific CD4(+) and CD8(+) immune responses are generated with a gp120-depleted, whole-killed HIV-1 immunogen with CpG immunostimulatory sequences of DNA

We examined the adjuvant effects of a synthetic CpG oligodeoxynucleotide im munostimulatory sequence (ISS) using a whole-killed, gp120-depleted HIV ant igen (HIV-1 antigen) in a Lewis rat model. We hypothesized that HIV-1-speci fic CD4(+) T helper (Th) immune responses could be enhanced when an ISS was combined with an HIV-1 antigen in incomplete Freund's adjuvant (IFA). We a lso reasoned that if such Th responses were sufficient, such a combination might also induce HIV-specific CD8(+) T cell immune responses. Here we demo nstrate that the HIV-1 antigen in IFA combined with ISS stimulates both CD4 (+) and CD8(+) HIV-specific immune responses as measured by interferon-gamm a (IFN-gamma) in the ELISPOT assay. A strong correlation between these CD4( +) and CD8(+) responses was demonstrated. Furthermore, we found that the HI V-1 antigen in IFA with ISS as an adjuvant stimulated strong antibody respo nses to core antigen (p24). These studies suggest that the combination of t he whole-killed, gp120-depleted HIV-1 antigen in IFA with ISS may be an ide al candidate to test in nonhuman primates and in human studies as a prevent ive HIV-1 vaccine.