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Zimmermann, Julie; van Haren, Simon D.; Diray-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

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  • Media type: E-Article
  • Title: Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
  • Contributor: Zimmermann, Julie; van Haren, Simon D.; Diray-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.
  • Published: Springer Science and Business Media LLC, 2023
  • Published in: npj Vaccines, 8 (2023) 1
  • Language: English
  • DOI: 10.1038/s41541-023-00781-0
  • ISSN: 2059-0105
  • Keywords: Pharmacology (medical) ; Infectious Diseases ; Pharmacology ; Immunology
  • Origination:
  • Footnote:
  • Description: AbstractClass-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.
  • Access State: Open Access