Effect of a Gp 120-depleted inactivated HIV-1 immunogen (REMUNE (TM)) on the control of nuclear factor Kappa-B activation, cytokine production and augmentation of HIV-1-specific cytotoxic T lymphocytes

To determine how REMUNETM affects the immune system we have investigated it s effect on the induction of NF-KB in purified activated T cells. NF-KB act ivation was evaluated by EMSA. The presence of REMUNETM inhibited NF-KB bin ding activity in the nucleus of T cells 4-hrs after activation. We are curr ently testing REMUNETM in a double blinded trial of REMUNE versus IFA coadm inistered with antiretrovirals. An immunological analysis was performed in a subset of 54 out the 243 HIV+ subjets included in the trial. At month 24, HIV-1-specific memory CTL precursors are strongly increased in REMUNE-Grou p. A significant increase of CD4 and CD8 memory T-cells, with a decrease of naive cells was observed in REMUNE Group. Lymphocyte proliferation and IFN -gamma production to HIV-1 antigen-stimulated PBMCs increased significantly in REMUNE as compared to IFA-Group. Only the REMUNE-group showed a good co rrelation between IFN-gamma and RANTES production, IFN-gamma and MIP-1 beta , and RANTES and MIP-I beta. These findings are the first to demostrate tha t REIMUNETM can provide an immunomodulatory effect in T-cell activation and enhance HIV-1-specific T-cell responses.