We have generated SIVDnef recombinants that contain the human IFN-g gene under the control of the SV40 early promoted. SIVsv-ifn contains the SV40 early promoted-IFN-g cassette in the sense orientation, whereas for SIVnfi-vs this insertion is in the anti-sense orientation. Only SIVsv-ifn expresses moderate levels of IFN-g, while cells infected with SIVnfi-vs manifested minimum activity . Rhesus macaques were given 2000 TCID50 of these viruses; cell-associated virus loads were determined in PBMCUs and lymph nodes (LN). Animals were challenged with100 AID50 of SIVmac251. Viral loads after challenge were much lower for animals that received live-attenuated vaccines than for the naive macaques; however, differences among the viral loads in immunized macaques were not statistically significant. One year after challenge all animals were still healthy. A new experiment studied effects of intravenous injection of vaccinia virus (VV) . Macaques were injected with 1 ml of RPMI containing 107 pfu of a Wyeth VV recombinant. One group received vSIV-VLP (a VV that expresses SIVgag and env), and another received vHug/SIV-VLP (a VV expressing human IFN-g and the same SIV antigens). Neither macaque inoculated with vSIV-VLP had noticeable problems or abnormal CBC. Of the two macaques inoculated with vHug/SIV-VLP, one had two days of reported poor appetite in the first two weeks post-inoculation and brief weight loss (from wich he rapidly recovered) at 2-3 weeks post-inoculation. This macaqueUs terminal CBC was within normal limits. The remaining macaque had no noticeable problems, but a terminal CBC showing mild anemia (which had been present pre-inoculation), marked decrease in lymphocytes, and slightly icteric plasma.