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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells. / Zimmermann, Julie; van Haren, Simon D.; Arce, Joann; Adriawan, Ignatius Ryan; Wørzner, Katharina; Krog, Ricki T.; Guleed, Safia; Hu, Tu; Mortensen, Rasmus; Dietrich, Jes; Solbak, Sara M.Ø.; Levy, Ofer; Christensen, Dennis; Pedersen, Gabriel K.

In: npj Vaccines, Vol. 8, No. 1, 189, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Zimmermann, J, van Haren, SD, Arce, J, Adriawan, IR, Wørzner, K, Krog, RT, Guleed, S, Hu, T, Mortensen, R, Dietrich, J, Solbak, SMØ, Levy, O, Christensen, D & Pedersen, GK 2023, 'Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells', npj Vaccines, vol. 8, no. 1, 189. https://doi.org/10.1038/s41541-023-00781-0

APA

Zimmermann, J., van Haren, S. D., Arce, J., Adriawan, I. R., Wørzner, K., Krog, R. T., Guleed, S., Hu, T., Mortensen, R., Dietrich, J., Solbak, S. M. Ø., Levy, O., Christensen, D., & Pedersen, G. K. (2023). Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells. npj Vaccines, 8(1), [189]. https://doi.org/10.1038/s41541-023-00781-0

Vancouver

Zimmermann J, van Haren SD, Arce J, Adriawan IR, Wørzner K, Krog RT et al. Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells. npj Vaccines. 2023;8(1). 189. https://doi.org/10.1038/s41541-023-00781-0

Author

Zimmermann, Julie ; van Haren, Simon D. ; Arce, Joann ; Adriawan, Ignatius Ryan ; Wørzner, Katharina ; Krog, Ricki T. ; Guleed, Safia ; Hu, Tu ; Mortensen, Rasmus ; Dietrich, Jes ; Solbak, Sara M.Ø. ; Levy, Ofer ; Christensen, Dennis ; Pedersen, Gabriel K. / Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells. In: npj Vaccines. 2023 ; Vol. 8, No. 1.

Bibtex

@article{5e0d1f5be2ae41ae951e93ac986b9a9d,
title = "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{\textregistered}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.",
author = "Julie Zimmermann and {van Haren}, {Simon D.} and Joann Arce and Adriawan, {Ignatius Ryan} and Katharina W{\o}rzner and Krog, {Ricki T.} and Safia Guleed and Tu Hu and Rasmus Mortensen and Jes Dietrich and Solbak, {Sara M.{\O}.} and Ofer Levy and Dennis Christensen and Pedersen, {Gabriel K.}",
note = "Authoe Correction: https://www.nature.com/articles/s41541-024-00804-4",
year = "2023",
doi = "10.1038/s41541-023-00781-0",
language = "English",
volume = "8",
journal = "npj Vaccines",
issn = "2059-0105",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells

AU - Zimmermann, Julie

AU - van Haren, Simon D.

AU - Arce, Joann

AU - Adriawan, Ignatius Ryan

AU - Wørzner, Katharina

AU - Krog, Ricki T.

AU - Guleed, Safia

AU - Hu, Tu

AU - Mortensen, Rasmus

AU - Dietrich, Jes

AU - Solbak, Sara M.Ø.

AU - Levy, Ofer

AU - Christensen, Dennis

AU - Pedersen, Gabriel K.

N1 - Authoe Correction: https://www.nature.com/articles/s41541-024-00804-4

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41541-023-00781-0

DO - 10.1038/s41541-023-00781-0

M3 - Journal article

C2 - 38135685

AN - SCOPUS:85180506970

VL - 8

JO - npj Vaccines

JF - npj Vaccines

SN - 2059-0105

IS - 1

M1 - 189

ER -

ID: 378766932