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

Charlotta Nilsson, Bo Hejdeman, Karina Godoy-Ramirez, Teghesti Tecleab, Gabriella Scarlatti, Andreas Bråve, Patricia L. Earl, Richard R. Stout, Merlin L. Robb, Robin J. Shattock, Gunnel Biberfeld, Eric Sandström, Britta Wahren

Research output: Contribution to journalArticle

22 Citations (Scopus)

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-1βand/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.

Original languageEnglish
Article numbere0131748
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 29 2015

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Electroporation
electroporation
Human immunodeficiency virus 1
HIV-1
HIV
DNA
T-cells
placebos
volunteers
T-lymphocytes
interleukin-2
Interleukin-2
vaccination
immune response
vaccines
Immunization
DNA Vaccines
antibodies
Antibodies
Placebos

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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. / Nilsson, Charlotta; Hejdeman, Bo; Godoy-Ramirez, Karina; Tecleab, Teghesti; Scarlatti, Gabriella; Bråve, Andreas; Earl, Patricia L.; Stout, Richard R.; Robb, Merlin L.; Shattock, Robin J.; Biberfeld, Gunnel; Sandström, Eric; Wahren, Britta.

In: PLoS One, Vol. 10, No. 6, e0131748, 29.06.2015.

Research output: Contribution to journalArticle

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 & Wahren, B 2015, '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', PLoS One, vol. 10, no. 6, e0131748. https://doi.org/10.1371/journal.pone.0131748
Nilsson, Charlotta ; Hejdeman, Bo ; Godoy-Ramirez, Karina ; Tecleab, Teghesti ; Scarlatti, Gabriella ; Bråve, Andreas ; Earl, Patricia L. ; Stout, Richard R. ; Robb, Merlin L. ; Shattock, Robin J. ; Biberfeld, Gunnel ; Sandström, Eric ; Wahren, Britta. / 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. In: PLoS One. 2015 ; Vol. 10, No. 6.
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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-1βand/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.",
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T1 - HIV-DNA given with or without intradermal electroporation is safe and highly immunogenic in healthy Swedish HIV-1 DNA/MVA vaccinees

T2 - A phase I randomized trial

AU - Nilsson, Charlotta

AU - Hejdeman, Bo

AU - Godoy-Ramirez, Karina

AU - Tecleab, Teghesti

AU - Scarlatti, Gabriella

AU - Bråve, Andreas

AU - Earl, Patricia L.

AU - Stout, Richard R.

AU - Robb, Merlin L.

AU - Shattock, Robin J.

AU - Biberfeld, Gunnel

AU - Sandström, Eric

AU - Wahren, Britta

PY - 2015/6/29

Y1 - 2015/6/29

N2 - 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-1βand/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.

AB - 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-1βand/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.

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