Evidence map›Paper›PMID 38135685›Full record

ArticleNPJ vaccines2023

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

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 and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in NPJ vaccines, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Julie Zimmermann *Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-6442-6439
Simon D van Haren *Precision Vaccines Program, Boston Children's Hospital, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-1791-0161
Joann Diray-ArcePrecision Vaccines Program, Boston Children's Hospital, Boston, MA, 02115, USA.
Ignatius Ryan AdriawanCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
Katharina WørznerCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-9430-4229
Ricki T KrogCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-0201-7207
Safia GuleedCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
Tu HuCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
Rasmus MortensenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-0177-3032
Jes DietrichCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-8536-0141
Sara M Ø SolbakDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Ofer LevyPrecision Vaccines Program, Boston Children's Hospital, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-5859-1945
Dennis ChristensenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-2382-8639
Gabriel K PedersenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. gakp@ssi.dk.ORCID http://orcid.org/0000-0001-6872-3975
Statens Serum Institut · DKBoston Children's Hospital · USBroad Institute · USUniversity of Copenhagen · DK

Funding

Small-molecule adjuvants to enhance the efficacy of flu vaccines in newborns and the elderly75N93019C00044 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2019 to 2023
$11.0M
NIAID NIH HHS 75N93019C00044NIAID NIH HHS HHSN272201800047C
6 · The paper itself

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.

Identifiers

PMID38135685
PMCPMC10746746
OpenAlexW4390106044

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.