title: Functional testing of an inhalable nanoparticle based influenza vaccine using a human precision cut lung slice technique.
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.
authors: Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
authors: Vanessa
authors: V
authors: Neuhaus
authors: Katharina
authors: K
authors: Schwarz
authors: Anna
authors: A
authors: Klee
authors: Sophie
authors: S
authors: Seehase
authors: Christine
authors: C
authors: Förster
authors: Olaf
authors: O
authors: Pfennig
authors: Danny
authors: D
authors: Jonigk
authors: Hans-Gerd
authors: HG
authors: Fieguth
authors: Wolfgang
authors: W
authors: Koch
authors: Gregor
authors: G
authors: Warnecke
authors: Vidadi
authors: V
authors: Yusibov
authors: Katherina
authors: K
authors: Sewald
authors: Armin
authors: A
authors: Braun
mesh_terms: D000280:Administration, Inhalation; D016207:Cytokines / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008168:Lung / Q000276:immunology / Q000473:pathology; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D018836:Inflammation Mediators; D007252:Influenza Vaccines; D058726:Nanoconjugates; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide
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