Functional Testing of an Inhalable Nanoparticle Based Influenza Vaccine Using a Human Precision Cut Lung Slice TechniqueReport as inadecuate




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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 ≥103 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.



Author: Vanessa Neuhaus, Katharina Schwarz, Anna Klee, Sophie Seehase, Christine Förster, Olaf Pfennig, Danny Jonigk, Hans-Gerd Fieguth,

Source: http://plos.srce.hr/



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