Evidence map›Paper›PMID 31654684›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2019

Co-encapsulation of synthetic lipidated TLR4 and TLR7/8 agonists in the liposomal bilayer results in a rapid, synergistic enhancement of vaccine-mediated humoral immunity.

Kristopher K Short, Shannon M Miller, Lois Walsh, Van Cybulski, Hélène Bazin, Jay T Evans, David Burkhart

Open access · greenAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. A novel cationic liposome-formulated toll like receptor (TLR) 7/8 agonist enhances the efficacy of a vaccine against fentanyl toxicity.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  7. Article
  8. TestingPharmaceutics · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  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 1 institution in 1 country.

Kristopher K ShortCenter for Translational Medicine, University of Montana, Missoula, MT 59812, USA; Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
Shannon M MillerCenter for Translational Medicine, University of Montana, Missoula, MT 59812, USA; Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
Lois WalshCenter for Translational Medicine, University of Montana, Missoula, MT 59812, USA; Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
Van CybulskiCenter for Translational Medicine, University of Montana, Missoula, MT 59812, USA; Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
Hélène BazinCenter for Translational Medicine, University of Montana, Missoula, MT 59812, USA; Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
Jay T EvansCenter for Translational Medicine, University of Montana, Missoula, MT 59812, USA; Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
David BurkhartCenter for Translational Medicine, University of Montana, Missoula, MT 59812, USA; Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA. Electronic address: david.burkhart@umontana.edu.
University of Montana · US

Funding

NIAID NIH HHS HHSN272200900036C
6 · The paper itself

Abstract

To increase vaccine immunogenicity, modern vaccines incorporate adjuvants, which serve to enhance immune cross-protection, improve humoral and cell-mediated immunity, and promote antigen dose sparing. Pattern recognition receptors (PRRs), including the Toll-like receptor (TLR) family are promising targets for development of agonist formulations for use as vaccine adjuvants. Combinations of co-delivered TLR4 and TLR7/8 ligands have been demonstrated to have synergistic effects on innate and adaptive immune response. Here, we create liposomes that stably co-encapsulate CRX-601, a synthetic TLR4 agonist, and UM-3004, a lipidated TLR7/8 agonist, within the liposomal bilayer in order to achieve co-delivery, allow tunable physical properties, and induce in vitro and in vivo immune synergy. Co-encapsulation demonstrates a synergistic increase in IL-12p70 cytokine output in vitro from treated human peripheral blood mononuclear cells (hPBMCs). Further, co-encapsulated formulations give significant improvement of early IgG2a antibody titers in BALB/c mice following primary vaccination when compared to single agonist or dual agonists delivered in separate liposomes. This work demonstrates that co-encapsulation of TLR4 and lipidated TLR7/8 agonists within the liposomal bilayer leads to innate and adaptive immune synergy which biases a Th1 immune response. Thus, liposomal co-encapsulation may be a useful and flexible tool for vaccine adjuvant formulation containing multiple TLR agonists.

Indexed as

Adjuvants, ImmunologicAnimalsDrug Delivery SystemsDrug SynergismFemaleHeterocyclic Compounds, 3-RingHumansImmunity, HumoralLeukocytes, MononuclearLiposomesMiceMice, Inbred BALB CMonosaccharidesTh1 CellsToll-Like Receptor 4Toll-Like Receptor 7Adjuvants, ImmunologicHeterocyclic Compounds, 3-RingLiposomesMonosaccharidesToll-Like Receptor 4Toll-Like Receptor 7Toll-Like Receptor 8VaccinesCo-deliveryInfluenza vaccineInfluenza virusLiposomeToll-like receptor (TLR)Vaccine adjuvant

Identifiers

PMID31654684
PMCPMC6980726
OpenAlexW2981533670

What OpenQuestion holds

Textmetadata
LicenceTDM
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.