ArticleJournal of controlled release : official journal of the Controlled Release Society2021
TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Mitophagy-mediated immune evasion: Shared strategies of pathogens.Redox biology · 2026Review
- Probing Immune Signatures of Conjugated Pattern Recognition Receptor Ligands Identifies Chimeras with Potent Adjuvant and Antitumor Activities.Journal of medicinal chemistry · 2026Article
- Immunostimulatory Pickering emulsion for oral vaccine delivery.International journal of pharmaceutics · 2025Article
- Fabrication of RIG-I-Activating Nanoparticles for Intratumoral Immunotherapy via Flash Nanoprecipitation.Molecular pharmaceutics · 2025Article
- Generation of an inflammatory niche in a hydrogel depot through recruitment of key immune cells improves efficacy of mRNA vaccines.Science advances · 2025Article
- A Dual-Adjuvanted Parenteral-Intranasal Subunit Nanovaccine generates Robust Systemic and Mucosal Immunity Against SARS-CoV-2 in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nanocarrier design for pathogen-inspired innate immune agonist delivery.Trends in immunology · 2024Review
- Article
- A Cancer Nanovaccine for Co-Delivery of Peptide Neoantigens and Optimized Combinations of STING and TLR4 Agonists.ACS nano · 2024Article
- Longitudinal analysis of influenza vaccination implicates regulation of RIG-I signaling by DNA methylation.Scientific reports · 2024Article
- Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-Based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses.Pharmaceutics · 2024Article
- Advances in protein subunit vaccines against H1N1/09 influenza.Frontiers in immunology · 2024Review
- Comb-structured mRNA vaccine tethered with short double-stranded RNA adjuvants maximizes cellular immunity for cancer treatment.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Single-cell epitope-transcriptomics reveal lung stromal and immune cell response kinetics to nanoparticle-delivered RIG-I and TLR4 agonists.Biomaterials · 2023Article
- Immunologically effective biomaterials-enhanced vaccines against infection of pathogenic microorganisms.Biosafety and health · 2023Review
- Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.Advanced drug delivery reviews · 2021Review
- Soluble and Microparticle-Based Delivery of TLR4 and TLR9 Agonists Differentially Modulate 3D Chemotaxis of Bone Marrow-Derived Dendritic Cells.Advanced healthcare materials · 2021Article
- Nucleic acid nanoparticles (NANPs) as molecular tools to direct desirable and avoid undesirable immunological effects.Advanced drug delivery reviews · 2021Review
- Promising Adjuvants and Platforms for Influenza Vaccine Development.Pharmaceutics · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Although the existing flu vaccines elicit strong antigen-specific antibody responses, they fail to provide effective, long term protection - partly due to the absence of robust cellular memory immunity. We hypothesized that co-administration of combination adjuvants, mirroring the flu-virus related innate signaling pathways, could elicit strong cellular immunity. Here, we show that the small molecule adjuvant R848 and the RNA adjuvant PUUC, targeting endosomal TLR7s and cytoplasmic RLRs respectively, when delivered together in polymer nanoparticles (NP), elicits a broadened immune responses in mouse bone marrow-derived dendritic cells (mBMDCs) and a synergistic response in both mouse and human plasmacytoid dendritic cells (pDCs). In mBMDCs, NP-R848-PUUC induced both NF-κB and interferon signaling. Interferon responses to co-delivered R848 and PUUC were additive in human peripheral blood mononuclear cells (PBMCs) and synergistic in human FLT3-differentiated mBMDCs and CAL-1 pDCs. Vaccination with NPs loaded with H1N1 Flu antigen, R848, and PUUC increased percentage of CD8+ T-cells in the lungs, percentage of antigen-specific CD4-T-cells in the spleen, and enhanced overall cytokine-secreting T cell percentages upon antigen restimulation. Also, in the spleen, T lymphopenia, especially after in vitro restimulation with dual adjuvants, was observed, indicating highly antigen-reactive T cells. Our results demonstrate that simultaneous engagement of TLR7 and RIG-I pathways using particulate carriers is a potential approach to improve cellular immunity in flu vaccination.
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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.