Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

EO Viegas, A Kroidl, PJ Munseri, M Missanga, C Nilsson, N Tembe, A Bauer, A Joachim, S Joseph, P Mann, C Geldmacher, S Fleck, W Stöhr, G Scarlatti, S Aboud, M Bakari, L Maboko, M Hoelscher, B Wahren, ML RobbJ Weber, S McCormack, G Biberfeld, IV Jani, E Sandström, E Lyamuya, TaMoVac study group

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Abstract

Background We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. Methods Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. Results Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p
Original languageEnglish
Article numbere0206838
JournalPLoS One
Volume13
Issue number11
DOIs
Publication statusPublished - 2018

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electroporation
Electroporation
Vaccines
immune response
HIV
vaccines
DNA
volunteers
Syringes
Lipid A
Volunteers
Viruses
Needles
vaccination
Vaccinia virus
Mozambique
Vaccination
syringes
Antigens
Peptides

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Viegas, EO., Kroidl, A., Munseri, PJ., Missanga, M., Nilsson, C., Tembe, N., ... group, T. S. (2018). Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design. PLoS One, 13(11), [e0206838]. https://doi.org/10.1371/journal.pone.0206838

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design. / Viegas, EO; Kroidl, A; Munseri, PJ; Missanga, M; Nilsson, C; Tembe, N; Bauer, A; Joachim, A; Joseph, S; Mann, P; Geldmacher, C; Fleck, S; Stöhr, W; Scarlatti, G; Aboud, S; Bakari, M; Maboko, L; Hoelscher, M; Wahren, B; Robb, ML; Weber, J; McCormack, S; Biberfeld, G; Jani, IV; Sandström, E; Lyamuya, E; group, TaMoVac study.

In: PLoS One, Vol. 13, No. 11, e0206838, 2018.

Research output: Contribution to journalArticle

Viegas, EO, Kroidl, A, Munseri, PJ, Missanga, M, Nilsson, C, Tembe, N, Bauer, A, Joachim, A, Joseph, S, Mann, P, Geldmacher, C, Fleck, S, Stöhr, W, Scarlatti, G, Aboud, S, Bakari, M, Maboko, L, Hoelscher, M, Wahren, B, Robb, ML, Weber, J, McCormack, S, Biberfeld, G, Jani, IV, Sandström, E, Lyamuya, E & group, TS 2018, 'Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design', PLoS One, vol. 13, no. 11, e0206838. https://doi.org/10.1371/journal.pone.0206838
Viegas, EO ; Kroidl, A ; Munseri, PJ ; Missanga, M ; Nilsson, C ; Tembe, N ; Bauer, A ; Joachim, A ; Joseph, S ; Mann, P ; Geldmacher, C ; Fleck, S ; Stöhr, W ; Scarlatti, G ; Aboud, S ; Bakari, M ; Maboko, L ; Hoelscher, M ; Wahren, B ; Robb, ML ; Weber, J ; McCormack, S ; Biberfeld, G ; Jani, IV ; Sandström, E ; Lyamuya, E ; group, TaMoVac study. / Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design. In: PLoS One. 2018 ; Vol. 13, No. 11.
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abstract = "Background We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. Methods Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. Results Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97{\%}. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66{\%} group I vs. 86{\%} group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95{\%}, 99{\%}, 79{\%}, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p",
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T1 - Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

AU - Viegas, EO

AU - Kroidl, A

AU - Munseri, PJ

AU - Missanga, M

AU - Nilsson, C

AU - Tembe, N

AU - Bauer, A

AU - Joachim, A

AU - Joseph, S

AU - Mann, P

AU - Geldmacher, C

AU - Fleck, S

AU - Stöhr, W

AU - Scarlatti, G

AU - Aboud, S

AU - Bakari, M

AU - Maboko, L

AU - Hoelscher, M

AU - Wahren, B

AU - Robb, ML

AU - Weber, J

AU - McCormack, S

AU - Biberfeld, G

AU - Jani, IV

AU - Sandström, E

AU - Lyamuya, E

AU - group, TaMoVac study

PY - 2018

Y1 - 2018

N2 - Background We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. Methods Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. Results Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p

AB - Background We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. Methods Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. Results Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p

U2 - 10.1371/journal.pone.0206838

DO - 10.1371/journal.pone.0206838

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e0206838

ER -