ArticlePloS one2013
Functional testing of an inhalable nanoparticle based influenza vaccine using a human precision cut lung slice technique.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Modeling Immunity In Vitro: Slices, Chips, and Engineered Tissues.Annual review of biomedical engineering · 2021Pooled it
- Regulation of T cell tissue residency and activation in human PCLS.Respiratory research · 2025Article
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Nanoparticle‑based antiviral strategies to combat the influenza virus (Review).Biomedical reports · 2024Review
- Multiscale stiffness of human emphysematous precision cut lung slices.Science advances · 2023Article
- Cryopreserved human precision-cut lung slices provide an immune competent pulmonary test system for "on-demand" use and long-term cultures.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Modeling Innate Antiviral Immunity in Physiological Context.Journal of molecular biology · 2022Review
- Precision-cut lung slices: A powerful ex vivo model to investigate respiratory infectious diseases.Molecular microbiology · 2022Review
- Rhinovirus-induced Human Lung Tissue Responses Mimic Chronic Obstructive Pulmonary Disease and Asthma Gene Signatures.American journal of respiratory cell and molecular biology · 2021Article
- Advanced Nanoparticle-Based Drug Delivery Systems and Their Cellular Evaluation for Non-Small Cell Lung Cancer Treatment.Cancers · 2021Review
- Organotypic Models of Lung Cancer.Current topics in microbiology and immunology · 2021Article
- Use of Precision-Cut Tissue Slices as a Translational Model to Study Host-Pathogen Interaction.Frontiers in veterinary science · 2021Review
- An Overview on Spray-Drying of Protein-Loaded Polymeric Nanoparticles for Dry Powder Inhalation.Pharmaceutics · 2020Review
- Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery.American journal of respiratory cell and molecular biology · 2020Review
- Modifying and IntegratingFrontiers in bioengineering and biotechnology · 2020Review
- The effects of oxygen concentration on cell death, anti-oxidant transcription, acute inflammation, and cell proliferation in precision-cut lung slices.Scientific reports · 2019Article
- Transcriptomic Analysis Reveals Priming of The Host Antiviral Interferon Signaling Pathway by BronchobiniInternational journal of molecular sciences · 2019Article
- The impact of nanomaterial characteristics on inhalation toxicity.Toxicology research · 2018Review
- Plant Virus Expression Vectors: A Powerhouse for Global Health.Biomedicines · 2017Review
- Evaluation of inflammatory and immune responses in long-term cultured human precision-cut lung slices.Human vaccines & immunotherapeutics · 2017Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed. In the present study we investigated the local toxicity and capacity of a new inhalable influenza vaccine to induce an antigen-specific recall response at the site of virus entry in human precision-cut lung slices (PCLS). This new vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1), produced in tobacco plants, and a silica nanoparticle (NP)-based drug delivery system. We found no local cellular toxicity of the vaccine within applicable concentrations. However higher concentrations of NP (≥10(3) µg/ml) dose-dependently decreased viability of human PCLS. Furthermore NP, not the protein, provoked a dose-dependent induction of TNF-α and IL-1β, indicating adjuvant properties of silica. In contrast, we found an antigen-specific induction of the T cell proliferation and differentiation cytokine, IL-2, compared to baseline level (152±49 pg/mg vs. 22±5 pg/mg), which could not be seen for the NP alone. Additionally, treatment with 10 µg/ml HAC1 caused a 6-times higher secretion of IFN-γ compared to baseline (602±307 pg/mg vs. 97±51 pg/mg). This antigen-induced IFN-γ secretion was further boosted by the adjuvant effect of silica NP for the formulated vaccine to a 12-fold increase (97±51 pg/mg vs. 1226±535 pg/mg). Thus we were able to show that the plant-produced vaccine induced an adequate innate immune response and re-activated an established antigen-specific T cell response within a non-toxic range in human PCLS at the site of virus entry.
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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.