HIV-Specific CD4 + and CD8 + Immune Responses Are Generated with a gp120-Depleted,Whole-Killed HIV-1 Immunogen with CpG Immunostimulatory Sequences of DNA

Abstract

We examined the adjuvant effects of a synthetic CpG oligodeoxynucleotide immunostimulatory sequence (ISS) using a whole-killed, gp120-depleted HIV antigen (HIV-1 antigen) in a Lewis rat model. We hypothesized that HIV-1-specific 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 also reasoned that if such Th responses were sufficient, such a combination might also induce HIV-specific CD8⁺ T cell immune responses. Here we demonstrate that the HIV-1 antigen in IFA combined with ISS stimulates both CD4⁺ and CD8⁺ HIV-specific immune responses as measured by interferon-γ (IFN-γ) in the ELISPOT assay. A strong correlation between these CD4⁺ and CD8⁺ responses was demonstrated. Furthermore, we found that the HIV-1 antigen in IFA with ISS as an adjuvant stimulated strong antibody responses to core antigen (p24). These studies suggest that the combination of the whole-killed, gp120-depleted HIV-1 antigen in IFA with ISS may be an ideal candidate to test in nonhuman primates and in human studies as a preventive HIV-1 vaccine.