ArticleJournal of nanobiotechnology2014
A nanoliposome delivery system to synergistically trigger TLR4 AND TLR7.
Article in Journal of nanobiotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
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- HIV Virion Capturing Liposomes for Therapeutic Vaccination.bioRxiv : the preprint server for biology · 2025Article
- SARS-CoV-2 conjugate vaccine elicits robust immune responses that can protect against evolving variants.Vaccine · 2025Article
- Multifunctional Nanomaterials: Recent Advancements in Cancer Therapeutics and Vaccines.Indian journal of microbiology · 2025Article
- The recent advances in vaccine adjuvants.Frontiers in immunology · 2025Review
- Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope.Scientific reports · 2023Article
- Using Dual Toll-like Receptor Agonism to Drive Th1-Biased Response in a Squalene- and α-Tocopherol-Containing Emulsion for a More Effective SARS-CoV-2 Vaccine.Pharmaceutics · 2022Article
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- Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.Advanced drug delivery reviews · 2021Review
- A splenic-targeted versatile antigen courier: iPSC wrapped in coalescent erythrocyte-liposome as tumor nanovaccine.Science advances · 2021Article
- Mimicking Pathogens to Augment the Potency of Liposomal Cancer Vaccines.Pharmaceutics · 2021Review
- Nanonutraceuticals: The New Frontier of Supplementary Food.Nanomaterials (Basel, Switzerland) · 2021Review
- Exploration of Pattern Recognition Receptor Agonists as Candidate Adjuvants.Frontiers in cellular and infection microbiology · 2021Review
- Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment.Acta pharmaceutica Sinica. B · 2020Review
- Nanoparticle cancer vaccines: Design considerations and recent advances.Asian journal of pharmaceutical sciences · 2020Review
- 3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope-specific plasma cells and humoral immunity in nonhuman primates.Science immunology · 2020Article
- Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules.Journal of nanobiotechnology · 2020Article
- Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, inVaccine: X · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent reports that TLR4 and TLR7 ligands can synergistically trigger Th1 biased immune responses suggest that an adjuvant that contains both ligands would be an excellent candidate for co-administration with vaccine antigens for which heavily Th1 biased responses are desired. Ligands of each of these TLRs generally have disparate biochemical properties, however, and straightforward co-formulation may represent an obstacle.
resultsWe show here that the TLR7 ligand, imiquimod, and the TLR4 ligand, GLA, synergistically trigger responses in human whole blood. We combined these ligands in an anionic liposomal formulation where the TLR7 ligand is in the interior of the liposome and the TLR4 ligand intercalates into the lipid bilayer. The new liposomal formulations are stable for at least a year and have an attractive average particle size of around 140 nm allowing sterile filtration. The synergistic adjuvant biases away from Th2 responses, as seen by significantly reduced IL-5 and enhanced interferon gamma production upon antigen-specific stimulation of cells from immunized mice, than any of the liposomal formulations with only one TLR agonist. Qualitative alterations in antibody responses in mice demonstrate that the adjuvant enhances Th1 adaptive immune responses above any adjuvant containing only a single TLR ligand as well.
conclusionWe now have a manufacturable, synergistic TLR4/TLR7 adjuvant that is made with excipients and agonists that are pharmaceutically acceptable and will have a straightforward path into human clinical trials.
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Registered trials
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.