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.