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 (≥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.
Highlights
Every year, seasonal influenza occurs as an infectious viral disease of the respiratory tract that is caused by RNA viruses of the Orthomyxoviridae family.Influenza viruses present serious health threats worldwide, being responsible for annual global epidemics causing several million cases of severe illness and deaths in higher risk groups [1]
We investigated the local toxicity of a new inhalable influenza vaccine as well as its potential to recall an immune response at the point of the virus settlement in human precision-cut lung slices (PCLS)
This study aimed to characterize a new respiratory influenza vaccine formulated with a NP-based drug delivery system
Summary
Seasonal influenza occurs as an infectious viral disease of the respiratory tract that is caused by RNA viruses of the Orthomyxoviridae family.Influenza viruses present serious health threats worldwide, being responsible for annual global epidemics causing several million cases of severe illness and deaths in higher risk groups [1]. There is a risk of losing vaccination efficacy due to the high mutation rate of the influenza virus [3]. This reduced protection against mutated virus subtypes became especially apparent during the H1N1 pandemic outbreak in 2009. A high frequency of interspecies transmission and reassortment of the virus make influenza infections highly unpredictable [7,8] In this context, there is only a short time frame for the production of adapted influenza vaccines, from the identification of the present virus strain to its outbreak in the population. Optimization of the application at the site of the virus entry may increase the vaccine efficiency and reduce the vaccine dosage enabling even a small-scale production to provide sufficient amounts of vaccines to the global market
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