ArticleProceedings of the National Academy of Sciences of the United States of America2021
Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Prolonged intratumoral treatment with TLR7/8 agonist R848 regulates the tumor immune microenvironment resulting in enhanced antitumor activity.Cancer biology & therapy · 2026Article
- Comparison of the adjuvant effect of AS01, AS03 and alum on the immune response to GMP-grade H5N1 antigen in guinea pigs.Scientific reports · 2026Article
- Gardiquimod Nanoemulsion Targets Cutaneous Leishmaniasis Lesions Reducing Systemic Toxicity and Parasite Burden.Advanced healthcare materials · 2026Article
- Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Immune Responses of Dendritic Cells to Zoonotic DNA and RNA Viruses.Veterinary sciences · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- Regulating Immune Responses Induced by PEGylated Messenger RNA-Lipid Nanoparticle Vaccine.Vaccines · 2024Review
- Article
- From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation.Science advances · 2024Article
- Harnessing innate immune pathways for therapeutic advancement in cancer.Signal transduction and targeted therapy · 2024Review
- Article
- Multi-omics for COVID-19: driving development of therapeutics and vaccines.National science review · 2023Review
- The role of TLR7 agonists in modulating COVID-19 severity in subjects with loss-of-function TLR7 variants.Scientific reports · 2023Article
- Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate.JCI insight · 2023Article
- Next-Generation Adjuvants: Applying Engineering Methods to Create and Evaluate Novel Immunological Responses.Pharmaceutics · 2023Article
- Article
- Pre-existing CD4 T cell help boosts antibody responses but has limited impact on germinal center, antigen-specific B cell frequencies after influenza infection.Frontiers in immunology · 2023Article
- Shaping Neonatal Immunization by Tuning the Delivery of Synergistic Adjuvants via Nanocarriers.ACS chemical biology · 2022Article
- Toll-Like Receptor Signaling in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Innate Immune Responses and the Potential Application Value of Toll-Like Receptor Immunomodulators in Patients With Coronavirus Disease 2019.Frontiers in microbiology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast to commonly used adjuvants, such as aluminum hydroxide, Toll-like receptor (TLR) agonists induced robust phenotypic and functional DC maturation. In a DC-lymphocyte coculture system, we investigated the ensuing immune reactions. While monophosphoryl lipid A synthetic, a TLR4 ligand, induced checkpoint inhibitors indicative for immune exhaustion, the TLR7/8 agonist Resiquimod (R848) induced prominent type-1 interferon and interleukin 6 responses and robust CTL, B-cell, and NK-cell proliferation, which is particularly suited for antiviral immune responses. The recently licensed COVID-19 vaccines, BNT162b and mRNA-1273, are both based on single-stranded RNA. Indeed, we could confirm that the cytokine profile induced by lipid-complexed RNA was almost identical to the pattern induced by R848. Although this awaits further investigation, our results suggest that their efficacy involves the highly efficient antiviral response pattern stimulated by the RNAs' TLR7/8 activation.
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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.