Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans
To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive response...
Ausführliche Beschreibung
Autor*in: |
Wivine Burny [verfasserIn] Andrea Callegaro [verfasserIn] Viviane Bechtold [verfasserIn] Frédéric Clement [verfasserIn] Sophie Delhaye [verfasserIn] Laurence Fissette [verfasserIn] Michel Janssens [verfasserIn] Geert Leroux-Roels [verfasserIn] Arnaud Marchant [verfasserIn] Robert A. van den Berg [verfasserIn] Nathalie Garçon [verfasserIn] Robbert van der Most [verfasserIn] Arnaud M. Didierlaurent [verfasserIn] On Behalf of the ECR-002 Study Group [verfasserIn] Isabelle Carletti [verfasserIn] Frédéric Clement [verfasserIn] Arnaud Didierlaurent [verfasserIn] Meral Esen [verfasserIn] Julian Gabor [verfasserIn] Edwige Haelterman [verfasserIn] Caroline Hervé [verfasserIn] Yves Horsmans [verfasserIn] Peter Kremsner [verfasserIn] Philippe Moris [verfasserIn] Tino F Schwarz [verfasserIn] Fernanda Tavares da Silva [verfasserIn] Pascale Van Belle [verfasserIn] Pierre Van Damme [verfasserIn] Dirk Zuchner [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2017 |
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Übergeordnetes Werk: |
In: Frontiers in Immunology - Frontiers Media S.A., 2011, 8(2017) |
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Übergeordnetes Werk: |
volume:8 ; year:2017 |
Links: |
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DOI / URN: |
10.3389/fimmu.2017.00943 |
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Katalog-ID: |
DOAJ009923012 |
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520 | |a To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. | ||
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10.3389/fimmu.2017.00943 doi (DE-627)DOAJ009923012 (DE-599)DOAJ65af7ce2d89547bb915bf9bedc2e9b49 DE-627 ger DE-627 rakwb eng RC581-607 Wivine Burny verfasserin aut Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. vaccine adjuvants AS01 AS03 AS04 innate immune response adaptive immune response Immunologic diseases. Allergy Andrea Callegaro verfasserin aut Viviane Bechtold verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Laurence Fissette verfasserin aut Michel Janssens verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Robert A. van den Berg verfasserin aut Nathalie Garçon verfasserin aut Robbert van der Most verfasserin aut Arnaud M. Didierlaurent verfasserin aut On Behalf of the ECR-002 Study Group verfasserin aut Viviane Bechtold verfasserin aut Wivine Burny verfasserin aut Andrea Callegaro verfasserin aut Isabelle Carletti verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Arnaud Didierlaurent verfasserin aut Meral Esen verfasserin aut Laurence Fissette verfasserin aut Julian Gabor verfasserin aut Nathalie Garçon verfasserin aut Edwige Haelterman verfasserin aut Caroline Hervé verfasserin aut Yves Horsmans verfasserin aut Michel Janssens verfasserin aut Peter Kremsner verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Philippe Moris verfasserin aut Tino F Schwarz verfasserin aut Fernanda Tavares da Silva verfasserin aut Pascale Van Belle verfasserin aut Pierre Van Damme verfasserin aut Robert A. van den Berg verfasserin aut Robbert van der Most verfasserin aut Dirk Zuchner verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00943 kostenfrei https://doaj.org/article/65af7ce2d89547bb915bf9bedc2e9b49 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00943/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 |
spelling |
10.3389/fimmu.2017.00943 doi (DE-627)DOAJ009923012 (DE-599)DOAJ65af7ce2d89547bb915bf9bedc2e9b49 DE-627 ger DE-627 rakwb eng RC581-607 Wivine Burny verfasserin aut Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. vaccine adjuvants AS01 AS03 AS04 innate immune response adaptive immune response Immunologic diseases. Allergy Andrea Callegaro verfasserin aut Viviane Bechtold verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Laurence Fissette verfasserin aut Michel Janssens verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Robert A. van den Berg verfasserin aut Nathalie Garçon verfasserin aut Robbert van der Most verfasserin aut Arnaud M. Didierlaurent verfasserin aut On Behalf of the ECR-002 Study Group verfasserin aut Viviane Bechtold verfasserin aut Wivine Burny verfasserin aut Andrea Callegaro verfasserin aut Isabelle Carletti verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Arnaud Didierlaurent verfasserin aut Meral Esen verfasserin aut Laurence Fissette verfasserin aut Julian Gabor verfasserin aut Nathalie Garçon verfasserin aut Edwige Haelterman verfasserin aut Caroline Hervé verfasserin aut Yves Horsmans verfasserin aut Michel Janssens verfasserin aut Peter Kremsner verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Philippe Moris verfasserin aut Tino F Schwarz verfasserin aut Fernanda Tavares da Silva verfasserin aut Pascale Van Belle verfasserin aut Pierre Van Damme verfasserin aut Robert A. van den Berg verfasserin aut Robbert van der Most verfasserin aut Dirk Zuchner verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00943 kostenfrei https://doaj.org/article/65af7ce2d89547bb915bf9bedc2e9b49 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00943/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 |
allfields_unstemmed |
10.3389/fimmu.2017.00943 doi (DE-627)DOAJ009923012 (DE-599)DOAJ65af7ce2d89547bb915bf9bedc2e9b49 DE-627 ger DE-627 rakwb eng RC581-607 Wivine Burny verfasserin aut Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. vaccine adjuvants AS01 AS03 AS04 innate immune response adaptive immune response Immunologic diseases. Allergy Andrea Callegaro verfasserin aut Viviane Bechtold verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Laurence Fissette verfasserin aut Michel Janssens verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Robert A. van den Berg verfasserin aut Nathalie Garçon verfasserin aut Robbert van der Most verfasserin aut Arnaud M. Didierlaurent verfasserin aut On Behalf of the ECR-002 Study Group verfasserin aut Viviane Bechtold verfasserin aut Wivine Burny verfasserin aut Andrea Callegaro verfasserin aut Isabelle Carletti verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Arnaud Didierlaurent verfasserin aut Meral Esen verfasserin aut Laurence Fissette verfasserin aut Julian Gabor verfasserin aut Nathalie Garçon verfasserin aut Edwige Haelterman verfasserin aut Caroline Hervé verfasserin aut Yves Horsmans verfasserin aut Michel Janssens verfasserin aut Peter Kremsner verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Philippe Moris verfasserin aut Tino F Schwarz verfasserin aut Fernanda Tavares da Silva verfasserin aut Pascale Van Belle verfasserin aut Pierre Van Damme verfasserin aut Robert A. van den Berg verfasserin aut Robbert van der Most verfasserin aut Dirk Zuchner verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00943 kostenfrei https://doaj.org/article/65af7ce2d89547bb915bf9bedc2e9b49 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00943/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 |
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10.3389/fimmu.2017.00943 doi (DE-627)DOAJ009923012 (DE-599)DOAJ65af7ce2d89547bb915bf9bedc2e9b49 DE-627 ger DE-627 rakwb eng RC581-607 Wivine Burny verfasserin aut Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. vaccine adjuvants AS01 AS03 AS04 innate immune response adaptive immune response Immunologic diseases. Allergy Andrea Callegaro verfasserin aut Viviane Bechtold verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Laurence Fissette verfasserin aut Michel Janssens verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Robert A. van den Berg verfasserin aut Nathalie Garçon verfasserin aut Robbert van der Most verfasserin aut Arnaud M. Didierlaurent verfasserin aut On Behalf of the ECR-002 Study Group verfasserin aut Viviane Bechtold verfasserin aut Wivine Burny verfasserin aut Andrea Callegaro verfasserin aut Isabelle Carletti verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Arnaud Didierlaurent verfasserin aut Meral Esen verfasserin aut Laurence Fissette verfasserin aut Julian Gabor verfasserin aut Nathalie Garçon verfasserin aut Edwige Haelterman verfasserin aut Caroline Hervé verfasserin aut Yves Horsmans verfasserin aut Michel Janssens verfasserin aut Peter Kremsner verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Philippe Moris verfasserin aut Tino F Schwarz verfasserin aut Fernanda Tavares da Silva verfasserin aut Pascale Van Belle verfasserin aut Pierre Van Damme verfasserin aut Robert A. van den Berg verfasserin aut Robbert van der Most verfasserin aut Dirk Zuchner verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00943 kostenfrei https://doaj.org/article/65af7ce2d89547bb915bf9bedc2e9b49 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00943/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 |
allfieldsSound |
10.3389/fimmu.2017.00943 doi (DE-627)DOAJ009923012 (DE-599)DOAJ65af7ce2d89547bb915bf9bedc2e9b49 DE-627 ger DE-627 rakwb eng RC581-607 Wivine Burny verfasserin aut Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. vaccine adjuvants AS01 AS03 AS04 innate immune response adaptive immune response Immunologic diseases. Allergy Andrea Callegaro verfasserin aut Viviane Bechtold verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Laurence Fissette verfasserin aut Michel Janssens verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Robert A. van den Berg verfasserin aut Nathalie Garçon verfasserin aut Robbert van der Most verfasserin aut Arnaud M. Didierlaurent verfasserin aut On Behalf of the ECR-002 Study Group verfasserin aut Viviane Bechtold verfasserin aut Wivine Burny verfasserin aut Andrea Callegaro verfasserin aut Isabelle Carletti verfasserin aut Frédéric Clement verfasserin aut Sophie Delhaye verfasserin aut Arnaud Didierlaurent verfasserin aut Meral Esen verfasserin aut Laurence Fissette verfasserin aut Julian Gabor verfasserin aut Nathalie Garçon verfasserin aut Edwige Haelterman verfasserin aut Caroline Hervé verfasserin aut Yves Horsmans verfasserin aut Michel Janssens verfasserin aut Peter Kremsner verfasserin aut Geert Leroux-Roels verfasserin aut Arnaud Marchant verfasserin aut Philippe Moris verfasserin aut Tino F Schwarz verfasserin aut Fernanda Tavares da Silva verfasserin aut Pascale Van Belle verfasserin aut Pierre Van Damme verfasserin aut Robert A. van den Berg verfasserin aut Robbert van der Most verfasserin aut Dirk Zuchner verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.00943 kostenfrei https://doaj.org/article/65af7ce2d89547bb915bf9bedc2e9b49 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.00943/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 |
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vaccine adjuvants AS01 AS03 AS04 innate immune response adaptive immune response Immunologic diseases. Allergy |
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Wivine Burny @@aut@@ Andrea Callegaro @@aut@@ Viviane Bechtold @@aut@@ Frédéric Clement @@aut@@ Sophie Delhaye @@aut@@ Laurence Fissette @@aut@@ Michel Janssens @@aut@@ Geert Leroux-Roels @@aut@@ Arnaud Marchant @@aut@@ Robert A. van den Berg @@aut@@ Nathalie Garçon @@aut@@ Robbert van der Most @@aut@@ Arnaud M. Didierlaurent @@aut@@ On Behalf of the ECR-002 Study Group @@aut@@ Isabelle Carletti @@aut@@ Frédéric Clement @@aut@@ Arnaud Didierlaurent @@aut@@ Meral Esen @@aut@@ Julian Gabor @@aut@@ Edwige Haelterman @@aut@@ Caroline Hervé @@aut@@ Yves Horsmans @@aut@@ Peter Kremsner @@aut@@ Philippe Moris @@aut@@ Tino F Schwarz @@aut@@ Fernanda Tavares da Silva @@aut@@ Pascale Van Belle @@aut@@ Pierre Van Damme @@aut@@ Dirk Zuchner @@aut@@ |
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2017-01-01T00:00:00Z |
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Wivine Burny Andrea Callegaro Viviane Bechtold Frédéric Clement Sophie Delhaye Laurence Fissette Michel Janssens Geert Leroux-Roels Arnaud Marchant Robert A. van den Berg Nathalie Garçon Robbert van der Most Arnaud M. Didierlaurent On Behalf of the ECR-002 Study Group Isabelle Carletti Frédéric Clement Arnaud Didierlaurent Meral Esen Julian Gabor Edwige Haelterman Caroline Hervé Yves Horsmans Peter Kremsner Philippe Moris Tino F Schwarz Fernanda Tavares da Silva Pascale Van Belle Pierre Van Damme Dirk Zuchner |
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different adjuvants induce common innate pathways that are associated with enhanced adaptive responses against a model antigen in humans |
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Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans |
abstract |
To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. |
abstractGer |
To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. |
abstract_unstemmed |
To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway. |
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title_short |
Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans |
url |
https://doi.org/10.3389/fimmu.2017.00943 https://doaj.org/article/65af7ce2d89547bb915bf9bedc2e9b49 http://journal.frontiersin.org/article/10.3389/fimmu.2017.00943/full https://doaj.org/toc/1664-3224 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ009923012</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230503015703.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230225s2017 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2017.00943</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ009923012</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ65af7ce2d89547bb915bf9bedc2e9b49</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Wivine Burny</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E &gt; AS03 &gt; AS04 &gt; Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">vaccine adjuvants</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">AS01</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">AS03</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">AS04</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">innate immune response</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">adaptive immune response</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Immunologic diseases. 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