ArticleThe Journal of clinical investigation2010
Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- Gene expression profiles in neurological tissues during West Nile virus infection: a critical meta-analysis.BMC genomics · 2018Pooled it
- Programmable Antigen-Specific Immunity via Self-Adjuvanting Nanovaccines Co-Delivering Immune Modulators.Angewandte Chemie (International ed. in English) · 2026Article
- Iterative selection of lipid nanoparticle vaccine adjuvants for rapid elicitation of tumoricidal CD8⁺ T cells.Bioactive materials · 2025Article
- TLR agonists as adjuvants for viral vaccines: mechanisms, applications, and future directions.Frontiers in microbiology · 2025Review
- Immunostimulatory effects of Toll-like receptor ligands as adjuvants in establishing a novel mouse model for pemphigus vulgaris.Clinical and translational medicine · 2024Article
- Designing and immunomolecular analysis of a new broad-spectrum multiepitope vaccine against divergent human papillomavirus types.PloS one · 2024Article
- Sex-biased immunogenicity of a mucosal subunit vaccine against SARS-CoV-2 in mice.Frontiers in immunology · 2024Article
- Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes.Discovery immunology · 2024Review
- The postbiotic potential ofFrontiers in microbiology · 2024Review
- Novel immunotherapeutic options for BCG-unresponsive high-risk non-muscle-invasive bladder cancer.Cancer medicine · 2023Review
- DC-targeting lentivectors for cancer immunotherapy.Immunotherapy advances · 2023Review
- Protection from COVID-19 disease in hamsters vaccinated with subunit SARS-CoV-2 S1 mucosal vaccines adjuvanted with different adjuvants.Frontiers in immunology · 2023Article
- Chemically augmented malaria sporozoites display an altered immunogenic profile.Frontiers in immunology · 2023Article
- TLR agonists as vaccine adjuvants in the prevention of viral infections: an overview.Frontiers in microbiology · 2023Review
- Action Mechanisms and Scientific Rationale of Using Nasal Vaccine (HeberNasvac) for the Treatment of Chronic Hepatitis B.Vaccines · 2022Review
- Therapeutic applications of toll-like receptors (TLRs) agonists in AML.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Rational Vaccinology: Harnessing Nanoscale Chemical Design for Cancer Immunotherapy.ACS central science · 2022Review
- Modulation of injectable hydrogel properties for slow co-delivery of influenza subunit vaccine components enhance the potency of humoral immunity.Journal of biomedical materials research. Part A · 2021Article
- Constant regulation for stable CD8 T-cell functional avidity and its possible implications for cancer immunotherapy.European journal of immunology · 2021Review
- Prolonged Codelivery of Hemagglutinin and a TLR7/8 Agonist in a Supramolecular Polymer-Nanoparticle Hydrogel Enhances Potency and Breadth of Influenza Vaccination.ACS biomaterials science & engineering · 2021Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
TLR ligands are promising candidates for the development of novel vaccine adjuvants that can elicit protective immunity against emerging infectious diseases. Adjuvants have been used most frequently to increase the quantity of an immune response. However, the quality of a T cell response can be more important than its quantity. Stimulating certain pairs of TLRs induces a synergistic response in terms of activating dendritic cells and eliciting/enhancing T cell responses through clonal expansion, which increases the number of responding T cells. Here, we have found that utilizing ligands for 3 TLRs (TLR2/6, TLR3, and TLR9) greatly increased the protective efficacy of vaccination with an HIV envelope peptide in mice when compared with using ligands for only any 2 of these TLRs; surprisingly, increased protection was induced without a marked increase in the number of peptide-specific T cells. Rather, the combination of these 3 TLR ligands augmented the quality of the T cell responses primarily by amplifying their functional avidity for the antigen, which was necessary for clearance of virus. The triple combination increased production of DC IL-15 along with its receptor, IL-15Ralpha, which contributed to high avidity, and decreased expression of programmed death-ligand 1 and induction of Tregs. Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses.
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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.