Safety, Tolerability, and Immunogenicity of Repeated Doses of DermaVir, a Candidate Therapeutic HIV Vaccine, in HIV-Infected Patients Receiving Combination Antiretroviral Therapy: Results of the ACTG 5176 Trial

被引:0
作者
Rodriguez, Benigno [1 ,2 ]
Asmuth, David M. [3 ]
Matining, Roy M. [4 ]
Spritzler, John [4 ]
Jacobson, Jeffrey M. [5 ]
Mailliard, Robbie B. [6 ]
Li, Xiao-Dong [3 ]
Martinez, Ana I. [7 ]
Tenorio, Allan R. [8 ]
Lori, Franco [9 ]
Lisziewicz, Julianna [10 ,11 ]
Yesmin, Suria [12 ]
Rinaldo, Charles R. [6 ]
Pollard, Richard B. [3 ]
机构
[1] Case Western Reserve Univ, Univ Hosp Cleveland, Div Infect Dis, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Univ Hosp Cleveland, Ctr AIDS Res, Cleveland, OH 44106 USA
[3] Univ Calif Davis, Med Ctr, Div Infect Dis, Sacramento, CA 95817 USA
[4] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA
[5] Drexel Univ, Coll Med, Div Infect Dis & HIV Med, Philadelphia, PA 19104 USA
[6] Univ Pittsburgh, Pittsburgh, PA USA
[7] NIAID, Div Aids, Bethesda, MD 20892 USA
[8] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA
[9] ViroStat Srl, Sassari, Italy
[10] Genet Immun, Budapest, Hungary
[11] Genet Immun, Mclean, VA USA
[12] Social & Sci Syst Inc, Silver Spring, MD USA
关键词
DermaVir; CTL responses; HIV therapeutic vaccines; HIV-specific immune responses; SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL RESPONSES; TYPE-1; HIV-1; EX-VIVO; IMMUNIZATION; REPLICATION; ACTIVATION; PROTECTION; INDUCTION; MACAQUES;
D O I
暂无
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: HIV-specific cellular immune responses are associated with control of viremia and delayed disease progression. An effective therapeutic vaccine could mimic these effects and reduce the need for continued antiretroviral therapy. DermaVir, a topically administered plasmid DNA-nanomedicine expressing HIV (CladeB) virus-like particles consisting of 15 antigens, induces predominantly central memory T-cell responses. Methods: Treated HIV-infected adults (HIV RNA <50 and CD4 >350) were randomized to placebo or escalating DermaVir doses (0.1 or 0.4 mg of plasmid DNA at weeks 1, 7, and 13 in the low-and intermediate-dose groups and 0.8 mg at weeks 0, 1, 6, 7, 12, and 13 in the high-dose group), n = 5-6 evaluable subjects per group. Immunogenicity was assessed by a 12-day cultured interferon-g enzyme-linked immunosorbent spot assay at baseline and at weeks 9, 17, and 37 using 1 Tat/Rev and 3 overlapping Gag peptide pools (p17, p24, and p15). Results: Groups were comparable at baseline. The study intervention was well tolerated, without dose-limiting toxicities. Most responses were highest at week 17 (4 weeks after last vaccination) when Gag p24 responses were significantly greater among intermediate-dose group compared with control subjects [median (IQR): 67,600 (5633-74,368) versus 1194 (9-1667)] net spot-forming units per million cells, P = 0.032. In the intermediate-dose group, there was also a marginal Gag p15 response increase from baseline to week 17 [2859 (1867-56,933), P = 0.06], and this change was significantly greater than in the placebo group [0 (2713 to 297), P = 0.016]. Conclusions: DermaVir administration was associated with a trend toward greater HIV-specific, predominantly central memory T-cell responses. The intermediate DermaVir dose tended to show the greatest immunogenicity, consistent with previous studies in different HIV-infected patient populations.
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收藏
页码:351 / 359
页数:9
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