Evidence map›Paper›PMID 16439533›Full record

ArticleJournal of virology2006

Multimeric soluble CD40 ligand and GITR ligand as adjuvants for human immunodeficiency virus DNA vaccines.

Geoffrey W Stone, Suzanne Barzee, Victoria Snarsky, Kristin Kee, Celsa A Spina, Xiao-Fang Yu, Richard S Kornbluth

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

51 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. GITR activationiScience · 2023
    Article
  5. Review
  6. Article
  7. Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.Journal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Principles of antibody-mediated TNF receptor activation.Cell death and differentiation · 2015
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Geoffrey W StoneDepartment of Medicine-0679, Stein Clinical Sciences Bldg., Room 304, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0679, USA. rkornbluth@ucsd.edu
Suzanne Barzee
Victoria Snarsky
Kristin Kee
Celsa A Spina
Xiao-Fang Yu
Richard S Kornbluth
University of California, San Diego · USJohns Hopkins University · USNational Institutes of Health · USVA San Diego Healthcare System · US

Funding

VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Maile Ann Young Karris · 1994 to 2026
$78.4M
HOPE Training GrantT32AI007384 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sara Gianella Weibel, Scott L Letendre · 1990 to 2026
$9.7M
TNFSF APC activators for HIV VaccinesR21AI052842 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI KORNBLUTH, RICHARD SYD · 2002 to 2003
$422k
NIAID NIH HHS P30 AI036214NIAID NIH HHS R21 AI052842NIAID NIH HHS R21AI52842NIAID NIH HHS T32 AI007384NIAID NIH HHS T32AI007384
6 · The paper itself

Abstract

For use in humans, human immunodeficiency virus (HIV) DNA vaccines may need to include immunostimulatory adjuvant molecules. CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant, but it has been difficult to use because it is normally expressed as a trimeric membrane molecule. Soluble trimeric forms of CD40L have been produced, but in vitro data indicate that multimeric, many-trimer forms of soluble CD40L are more active. This multimerization requirement was evaluated in mice using plasmids that encoded either 1-trimer, 2-trimer, or 4-trimer soluble forms of CD40L. Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion with the body of surfactant protein D was used to produce the 4-trimer form. Using plasmids for secreted HIV-1 antigens Gag and Env, soluble CD40L was active as an adjuvant in direct proportion to the valence of the trimers (1 < 2 < 4). These CD40L-augmented DNA vaccines elicited strong CD8(+) T-cell responses but did not elicit significant CD4(+) T-cell or antibody responses. To test the applicability of the multimeric fusion protein approach to other TNFSFs, a 4-trimer construct for the ligand of glucocorticoid-induced TNF family-related receptor (GITR) was also prepared. Multimeric soluble GITR ligand (GITRL) augmented the CD8(+) T-cell, CD4(+) T-cell, and antibody responses to DNA vaccination. In summary, multimeric CD40L and GITRL are new adjuvants for DNA vaccines. Plasmids for expressing multimeric TNFSF fusion proteins permit the rapid testing of TNFSF molecules in vivo.

Indexed as

Adjuvants, ImmunologicAdiponectinAIDS VaccinesAnimalsCD40 LigandCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFemaleGene Products, envGene Products, gagHIV-1HIV AntibodiesImmunologic MemoryInterferon-gammaMiceAdiponectinAdipoq protein, mouseAdjuvants, ImmunologicAIDS VaccinesCD40 LigandGene Products, envGene Products, gagHIV AntibodiesInterferon-gammaPulmonary Surfactant-Associated Protein DRecombinant Fusion ProteinsTnfsf18 protein, mouseTumor Necrosis FactorsVaccines, DNA

Identifiers

PMID16439533
PMCPMC1367159
OpenAlexW2104643966

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.