Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells

Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationi...
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Autor*in:	Julie Zimmermann [verfasserIn] Simon D. van Haren [verfasserIn] Joann Diray-Arce [verfasserIn] Ignatius Ryan Adriawan [verfasserIn] Katharina Wørzner [verfasserIn] Ricki T. Krog [verfasserIn] Safia Guleed [verfasserIn] Tu Hu [verfasserIn] Rasmus Mortensen [verfasserIn] Jes Dietrich [verfasserIn] Sara M. Ø. Solbak [verfasserIn] Ofer Levy [verfasserIn] Dennis Christensen [verfasserIn] Gabriel K. Pedersen [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: npj Vaccines - Nature Portfolio, 2017, 8(2023), 1, Seite 12
Übergeordnetes Werk:	volume:8 ; year:2023 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41541-023-00781-0

Katalog-ID:	DOAJ097670286

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520			\|a Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.
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allfields	10.1038/s41541-023-00781-0 doi (DE-627)DOAJ097670286 (DE-599)DOAJb2a5b6ac83564fccb7d1fc8c4727c789 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Julie Zimmermann verfasserin aut Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Simon D. van Haren verfasserin aut Joann Diray-Arce verfasserin aut Ignatius Ryan Adriawan verfasserin aut Katharina Wørzner verfasserin aut Ricki T. Krog verfasserin aut Safia Guleed verfasserin aut Tu Hu verfasserin aut Rasmus Mortensen verfasserin aut Jes Dietrich verfasserin aut Sara M. Ø. Solbak verfasserin aut Ofer Levy verfasserin aut Dennis Christensen verfasserin aut Gabriel K. Pedersen verfasserin aut In npj Vaccines Nature Portfolio, 2017 8(2023), 1, Seite 12 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:8 year:2023 number:1 pages:12 https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/article/b2a5b6ac83564fccb7d1fc8c4727c789 kostenfrei https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 2023 1 12
spelling	10.1038/s41541-023-00781-0 doi (DE-627)DOAJ097670286 (DE-599)DOAJb2a5b6ac83564fccb7d1fc8c4727c789 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Julie Zimmermann verfasserin aut Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Simon D. van Haren verfasserin aut Joann Diray-Arce verfasserin aut Ignatius Ryan Adriawan verfasserin aut Katharina Wørzner verfasserin aut Ricki T. Krog verfasserin aut Safia Guleed verfasserin aut Tu Hu verfasserin aut Rasmus Mortensen verfasserin aut Jes Dietrich verfasserin aut Sara M. Ø. Solbak verfasserin aut Ofer Levy verfasserin aut Dennis Christensen verfasserin aut Gabriel K. Pedersen verfasserin aut In npj Vaccines Nature Portfolio, 2017 8(2023), 1, Seite 12 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:8 year:2023 number:1 pages:12 https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/article/b2a5b6ac83564fccb7d1fc8c4727c789 kostenfrei https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 2023 1 12
allfields_unstemmed	10.1038/s41541-023-00781-0 doi (DE-627)DOAJ097670286 (DE-599)DOAJb2a5b6ac83564fccb7d1fc8c4727c789 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Julie Zimmermann verfasserin aut Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Simon D. van Haren verfasserin aut Joann Diray-Arce verfasserin aut Ignatius Ryan Adriawan verfasserin aut Katharina Wørzner verfasserin aut Ricki T. Krog verfasserin aut Safia Guleed verfasserin aut Tu Hu verfasserin aut Rasmus Mortensen verfasserin aut Jes Dietrich verfasserin aut Sara M. Ø. Solbak verfasserin aut Ofer Levy verfasserin aut Dennis Christensen verfasserin aut Gabriel K. Pedersen verfasserin aut In npj Vaccines Nature Portfolio, 2017 8(2023), 1, Seite 12 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:8 year:2023 number:1 pages:12 https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/article/b2a5b6ac83564fccb7d1fc8c4727c789 kostenfrei https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 2023 1 12
allfieldsGer	10.1038/s41541-023-00781-0 doi (DE-627)DOAJ097670286 (DE-599)DOAJb2a5b6ac83564fccb7d1fc8c4727c789 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Julie Zimmermann verfasserin aut Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Simon D. van Haren verfasserin aut Joann Diray-Arce verfasserin aut Ignatius Ryan Adriawan verfasserin aut Katharina Wørzner verfasserin aut Ricki T. Krog verfasserin aut Safia Guleed verfasserin aut Tu Hu verfasserin aut Rasmus Mortensen verfasserin aut Jes Dietrich verfasserin aut Sara M. Ø. Solbak verfasserin aut Ofer Levy verfasserin aut Dennis Christensen verfasserin aut Gabriel K. Pedersen verfasserin aut In npj Vaccines Nature Portfolio, 2017 8(2023), 1, Seite 12 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:8 year:2023 number:1 pages:12 https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/article/b2a5b6ac83564fccb7d1fc8c4727c789 kostenfrei https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 2023 1 12
allfieldsSound	10.1038/s41541-023-00781-0 doi (DE-627)DOAJ097670286 (DE-599)DOAJb2a5b6ac83564fccb7d1fc8c4727c789 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Julie Zimmermann verfasserin aut Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Simon D. van Haren verfasserin aut Joann Diray-Arce verfasserin aut Ignatius Ryan Adriawan verfasserin aut Katharina Wørzner verfasserin aut Ricki T. Krog verfasserin aut Safia Guleed verfasserin aut Tu Hu verfasserin aut Rasmus Mortensen verfasserin aut Jes Dietrich verfasserin aut Sara M. Ø. Solbak verfasserin aut Ofer Levy verfasserin aut Dennis Christensen verfasserin aut Gabriel K. Pedersen verfasserin aut In npj Vaccines Nature Portfolio, 2017 8(2023), 1, Seite 12 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:8 year:2023 number:1 pages:12 https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/article/b2a5b6ac83564fccb7d1fc8c4727c789 kostenfrei https://doi.org/10.1038/s41541-023-00781-0 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_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 2023 1 12
language	English
source	In npj Vaccines 8(2023), 1, Seite 12 volume:8 year:2023 number:1 pages:12
sourceStr	In npj Vaccines 8(2023), 1, Seite 12 volume:8 year:2023 number:1 pages:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	npj Vaccines
authorswithroles_txt_mv	Julie Zimmermann @@aut@@ Simon D. van Haren @@aut@@ Joann Diray-Arce @@aut@@ Ignatius Ryan Adriawan @@aut@@ Katharina Wørzner @@aut@@ Ricki T. Krog @@aut@@ Safia Guleed @@aut@@ Tu Hu @@aut@@ Rasmus Mortensen @@aut@@ Jes Dietrich @@aut@@ Sara M. Ø. Solbak @@aut@@ Ofer Levy @@aut@@ Dennis Christensen @@aut@@ Gabriel K. Pedersen @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	87811839X
id	DOAJ097670286
language_de	englisch
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callnumber-first	R - Medicine
author	Julie Zimmermann
spellingShingle	Julie Zimmermann misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
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topic_title	RC581-607 RC254-282 Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
topic	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
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title_full	Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
author_sort	Julie Zimmermann
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author_browse	Julie Zimmermann Simon D. van Haren Joann Diray-Arce Ignatius Ryan Adriawan Katharina Wørzner Ricki T. Krog Safia Guleed Tu Hu Rasmus Mortensen Jes Dietrich Sara M. Ø. Solbak Ofer Levy Dennis Christensen Gabriel K. Pedersen
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author-letter	Julie Zimmermann
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title_sort	co-adjuvanting dda/tdb liposomes with a tlr7 agonist allows for igg2a/c class-switching in the absence of th1 cells
callnumber	RC581-607
title_auth	Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
abstract	Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.
abstractGer	Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.
abstract_unstemmed	Abstract Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.
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title_short	Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
url	https://doi.org/10.1038/s41541-023-00781-0 https://doaj.org/article/b2a5b6ac83564fccb7d1fc8c4727c789 https://doaj.org/toc/2059-0105
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author2	Simon D. van Haren Joann Diray-Arce Ignatius Ryan Adriawan Katharina Wørzner Ricki T. Krog Safia Guleed Tu Hu Rasmus Mortensen Jes Dietrich Sara M. Ø. Solbak Ofer Levy Dennis Christensen Gabriel K. Pedersen
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