Hiv-Dna Given With Or Without Intradermal Electroporation Is Safe And Highly Immunogenic In Healthy Swedish Hiv-1 Dna/Mva Vaccinees: A Phase I Randomized Trial

BackgroundWe compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers.MethodsHIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n= 16) or without (n= 9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVACMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA.ResultsThe ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-. ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p= 0.6158). The first HIV-MVA or HIV-MVA+ gp140 vaccination increased the IFN-. ELISpot response rate to 18/19 (95%). CD4(+) and/or CD8(+) T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4(+) and CD8(+) T cell response was noted, with 78% and 71% responders, respectively. IFN-. and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8(+) response to Gag was broader with expression of IFN-gamma, IL-2, MIP-1 beta and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients.ConclusionIntradermal electroporation of HIV-DNA was well tolerated. Strong cell-and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use.