Abstract: PDF OnlyG-111 DNA prime/subunit boost using SIVE660 based rhFLSC yields 75% efficacy against cross clade SIVmac251 intrarectal challengeFouts, Timothy*; Prado, Ilia*; Bobb, Kathryn*; Schwartz, Jennifer*; Bagley, Kenneth*; Xu, Rong*; Otya-Setlik, Ayuko*; Egan, Michael*; Eldridge, John*; Montefiori, David†; LaBranche, Celia†; Pal, Ranajit‡; Pavlakis, George§; Felber, Barbra§; Franchini, Genoveffa§; Gordon, Shari§; Vaccari, Monica§; Lewis, George‖; Devico, Anthony‖; Gallo, Robert¶Author Information *Profectus Biosciences; †Duke University Medical Center; ‡Advanced Bioscience Laboratories; §National Institutes of Health; ‖University of Maryland; and ¶Institute for Human Virology, University of Maryland JAIDS Journal of Acquired Immune Deficiency Syndromes: January 2016 - Volume 71 - Issue - p 69 doi: 10.1097/01.qai.0000479705.71198.09 Free Metrics Abstract An effective vaccine for HIV still remains elusive. Our previous studies showed that a protein-based FLSC (a genetic fusion of gp120 and CD4) protected macaques against repeat rectal challenges with SHIV162P3 but efficacy was low. We hypothesized that DNA would provide a superior prime to a subunit boost than subunit alone and that the adjuvants IL-12 and/or LTA1 would improve priming. FLSC delivery regimens were evaluated in a challenge model using SIVsmE543 antigens and a cross clade challenge with SIVmac251. Eight macaques/group were immunized with DNA expressing a gag/pol fusion and FLSC with/without LTA1, IL-12 or LTA1+IL-12 by electroporation on weeks 0, 4 and 8. Booster immunizations of 300 μg of FLSCsmCG7V/alum were given at week 42. Two weeks later, animals were weekly challenged rectally 10 times with SIVmac251. Immune measures were compared using T tests (parametric) or Mann-Whitney Rank Sum Tests (non-parametric). Infection rates were compared using Log Rank tests. The DNA/IL-12 prime regimen provided 75% efficacy compared to the same regimen without IL-12. Efficacy did not correlate with antibody binding or neutralizing titers to Tier 1 SIVmac251 whereas ADCC titers and antibody binding ratios of FcgR3/FcgR1 correlated with protection, provided T cell responses were low. The DNA/LTA1/IL-12 regimen generated substantially superior CMI responses, but showed no protection. These results suggest that vaccines generating ADCC capable antibodies with high FcgR3/FcgR1 ratios that evoke minimal T cell responses may be the most protective. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.