Boosting with subtype C CN54rgp140 protein adjuvanted with glucopyranosyl lipid adjuvant after priming with HIV-DNA and HIV-MVA is safe and enhances immune responses: A phase I trial

Agricola Joachim, Asli Bauer, Sarah Joseph, Christof Geldmacher, Patricia J. Munseri, Said Aboud, Marco Missanga, Philipp Mann, Britta Wahren, Guido Ferrari, Victoria R. Polonis, Merlin L. Robb, Jonathan Weber, Roger Tatoud, Leonard Maboko, Michael Hoelscher, Eligius F. Lyamuya, Gunnel Biberfeld, Eric Sandström, Arne Kroidl & 3 others Muhammad Bakari, Charlotta Nilsson, Sheena McCormack

Research output: Research - peer-reviewArticle

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Abstract

Background: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). Methods: Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/ GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart. Results: The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01-AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07). Conclusion: We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA. Trial Registration: International Clinical Trials Registry PACTR2010050002122368.

LanguageEnglish (US)
Article numbere0155702
JournalPLoS ONE
Volume11
Issue number5
DOIs
StatePublished - May 1 2016

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adjuvants
immunization
immune response
antibodies
DNA
lipids
proteins
Protein C
HIV
Lipids
Immunization
Antibodies
volunteers
Assays
Antibody Formation
Volunteers
neutralization tests
cytotoxicity
vaccination
vaccines

ASJC Scopus subject areas

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

Cite this

Boosting with subtype C CN54rgp140 protein adjuvanted with glucopyranosyl lipid adjuvant after priming with HIV-DNA and HIV-MVA is safe and enhances immune responses : A phase I trial. / Joachim, Agricola; Bauer, Asli; Joseph, Sarah; Geldmacher, Christof; Munseri, Patricia J.; Aboud, Said; Missanga, Marco; Mann, Philipp; Wahren, Britta; Ferrari, Guido; Polonis, Victoria R.; Robb, Merlin L.; Weber, Jonathan; Tatoud, Roger; Maboko, Leonard; Hoelscher, Michael; Lyamuya, Eligius F.; Biberfeld, Gunnel; Sandström, Eric; Kroidl, Arne; Bakari, Muhammad; Nilsson, Charlotta; McCormack, Sheena.

In: PLoS ONE, Vol. 11, No. 5, e0155702, 01.05.2016.

Research output: Research - peer-reviewArticle

Joachim, A, Bauer, A, Joseph, S, Geldmacher, C, Munseri, PJ, Aboud, S, Missanga, M, Mann, P, Wahren, B, Ferrari, G, Polonis, VR, Robb, ML, Weber, J, Tatoud, R, Maboko, L, Hoelscher, M, Lyamuya, EF, Biberfeld, G, Sandström, E, Kroidl, A, Bakari, M, Nilsson, C & McCormack, S 2016, 'Boosting with subtype C CN54rgp140 protein adjuvanted with glucopyranosyl lipid adjuvant after priming with HIV-DNA and HIV-MVA is safe and enhances immune responses: A phase I trial' PLoS ONE, vol 11, no. 5, e0155702. DOI: 10.1371/journal.pone.0155702
Joachim, Agricola ; Bauer, Asli ; Joseph, Sarah ; Geldmacher, Christof ; Munseri, Patricia J. ; Aboud, Said ; Missanga, Marco ; Mann, Philipp ; Wahren, Britta ; Ferrari, Guido ; Polonis, Victoria R. ; Robb, Merlin L. ; Weber, Jonathan ; Tatoud, Roger ; Maboko, Leonard ; Hoelscher, Michael ; Lyamuya, Eligius F. ; Biberfeld, Gunnel ; Sandström, Eric ; Kroidl, Arne ; Bakari, Muhammad ; Nilsson, Charlotta ; McCormack, Sheena. / Boosting with subtype C CN54rgp140 protein adjuvanted with glucopyranosyl lipid adjuvant after priming with HIV-DNA and HIV-MVA is safe and enhances immune responses : A phase I trial. In: PLoS ONE. 2016 ; Vol. 11, No. 5.
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title = "Boosting with subtype C CN54rgp140 protein adjuvanted with glucopyranosyl lipid adjuvant after priming with HIV-DNA and HIV-MVA is safe and enhances immune responses: A phase I trial",
abstract = "Background: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). Methods: Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/ GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart. Results: The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01-AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07). Conclusion: We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA. Trial Registration: International Clinical Trials Registry PACTR2010050002122368.",
author = "Agricola Joachim and Asli Bauer and Sarah Joseph and Christof Geldmacher and Munseri, {Patricia J.} and Said Aboud and Marco Missanga and Philipp Mann and Britta Wahren and Guido Ferrari and Polonis, {Victoria R.} and Robb, {Merlin L.} and Jonathan Weber and Roger Tatoud and Leonard Maboko and Michael Hoelscher and Lyamuya, {Eligius F.} and Gunnel Biberfeld and Eric Sandström and Arne Kroidl and Muhammad Bakari and Charlotta Nilsson and Sheena McCormack",
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T1 - Boosting with subtype C CN54rgp140 protein adjuvanted with glucopyranosyl lipid adjuvant after priming with HIV-DNA and HIV-MVA is safe and enhances immune responses

T2 - PLoS One

AU - Joachim,Agricola

AU - Bauer,Asli

AU - Joseph,Sarah

AU - Geldmacher,Christof

AU - Munseri,Patricia J.

AU - Aboud,Said

AU - Missanga,Marco

AU - Mann,Philipp

AU - Wahren,Britta

AU - Ferrari,Guido

AU - Polonis,Victoria R.

AU - Robb,Merlin L.

AU - Weber,Jonathan

AU - Tatoud,Roger

AU - Maboko,Leonard

AU - Hoelscher,Michael

AU - Lyamuya,Eligius F.

AU - Biberfeld,Gunnel

AU - Sandström,Eric

AU - Kroidl,Arne

AU - Bakari,Muhammad

AU - Nilsson,Charlotta

AU - McCormack,Sheena

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Background: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). Methods: Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/ GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart. Results: The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01-AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07). Conclusion: We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA. Trial Registration: International Clinical Trials Registry PACTR2010050002122368.

AB - Background: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). Methods: Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/ GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart. Results: The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01-AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07). Conclusion: We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA. Trial Registration: International Clinical Trials Registry PACTR2010050002122368.

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