1. 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.
- Author
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Nilsson C, Hejdeman B, Godoy-Ramirez K, Tecleab T, Scarlatti G, Bråve A, Earl PL, Stout RR, Robb ML, Shattock RJ, Biberfeld G, Sandström E, and Wahren B
- Subjects
- AIDS Vaccines adverse effects, Adult, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibody-Dependent Cell Cytotoxicity, Enzyme-Linked Immunospot Assay, Female, HIV Antibodies blood, HIV Antibodies immunology, HIV Infections immunology, HIV Infections prevention & control, Healthy Volunteers, Humans, Immunity, Cellular immunology, Immunity, Humoral immunology, Injections, Intradermal, Interferon-gamma biosynthesis, Lymphocyte Activation immunology, Male, Sweden, Vaccination, Vaccines, DNA adverse effects, Young Adult, AIDS Vaccines administration & dosage, Electroporation, HIV-1 genetics, HIV-1 immunology, Vaccines, DNA administration & dosage
- Abstract
Background: We 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., Methods: HIV-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 MVA-CMDR 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., Results: The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ 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-γ 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-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β 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., Conclusion: Intradermal 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., Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.
- Published
- 2015
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