DermaVir as a therapeutic vaccination strategy for HIV infection: results from ACTG protocol A5176
Background: DermaVir candidate therapeutic vaccine is a topically-administered pDNA-nanomedicine expressing HIV(CladeB) virus-like particles consisting of 15 antigens.
Methods: Treated HIV-infected adults (VL< 50, CD4>350) were randomized to placebo or three increasing DermaVir doses, n=5-6 evaluable subjects/group. Analyses were exploratory and not powered for immunogenicity. Both lower-dose groups received DermaVir at weeks 1/7/13; the highest-dose group at weeks 0/1/6/7/12/13. Results (*p< 0.2; **p< 0.1) are median SFU/million cells, of standard overnight and cultured IFN-γ ELISPOT assays, at baseline and post-vaccine time-points (PVT) 9/17/37 weeks, using one Tat/Rev and three overlapping Gag peptide pools (p17, p24, p15). The cultured assay detects HIV-specific precursor T-cells with high proliferative capacity (PHPC).
Results: Groups were comparable. Standard ELISPOT responses at PVTs tended to be higher in the combined DermaVir vs. the placebo group for p17 (weeks 9, 17, 37: 220 vs. 165, 213 vs. 207, 247 vs. 56), p24 (316 vs. 95*, 267 vs. 168, 305 vs. 28**), and p15 (119 vs. 92, 95 vs. 102, 112 vs. 95), but not Tat/Rev (23 vs. 45, 20 vs. 18, 13 vs. 29). PHPC responses showed a similar pattern at weeks 9 and 17 to p24 (1635 vs. 813, 2179 vs. 701* and 2427 vs. 294**), p15 (947 vs. 833, 2055 vs. 1352, 285 vs. 892) and Tat/Rev (566 vs. 84, 232 vs. 22, 0 vs. 35). Both assays showed a similar trend toward higher responses in the DermaVir group comparing AUCs (p≥0.18). The above differences were not statistically significant. The within-subject maximum PHPC AUC (weeks 0-37) of the three Gag pools was significantly greater in the intermediate-dose group (0.4 mg pDNA) vs. the placebo group (p=0.03).
Conclusions: DermaVir showed a trend toward greater HIV-specific T-cell responses in virologically-suppressed patients. The medium DermaVir dose tended to show the greatest effect, consistent with two previous studies in different HIV-infected patient populations.
B. Rodriguez1, D. Asmuth2, R. Matining3, J. Spritzler3, R. Mailliard4, C. Rinaldo4, J. Jacobson5, L. Xiao-Dong2, S. Read6, A. Martinez6, A. Tenorio7, F. Lori8, J. Lisziewicz9, R. Pollard2
1Case Western Reserve University, Cleveland, United States, 2University of California Davis, Sacramento, United States, 3Harvard School of Public Health, Boston, United States, 4University of Pittsburgh, Pittsburgh, United States, 5Drexel University, Philadelphia, United States, 6National Institute of Allergy and Infectious Diseases, Bethesda, United States, 7Rush University School of Medicine, Chicago, United States, 8ViroStatics srl, Sassari, Italy, 9Genetic Immunity, Budapest, Hungary