Preclinical evaluation of the Helicobacter pylori molecule vacuolating cytotoxin A (VacA) as a therapeutic approach for allergic airway disease

• Applicants: Dr. Sebastian Reuter; Professor Dr. Christian Taube
• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 434099933

Aim of the current project is the preclinical evaluation of the Helicobacter pylori molecule vacuolating cytotoxin A (VacA) as a therapeutic approach for allergic airway disease. Therapeutic effectiveness and mode of action of the molecule will be analyzed using murine in vivo and in vitro experiments. The effectiveness in humans and the suitability as a future therapeutic will be confirmed by the use of human in vitro experiments and the model of the humanized mice.Aim 1: Evaluation of the therapeutic effectiveness of a VacA treatment in the animal model. Here, dose response testing will be performed and the most effective application route will be identified. The therapeutic impact of the treatment will be validated in secondary and chronic challenge models of the airway disease. Beside the assessment of hallmarks of asthma (airway hyperresponsiveness, inflammation in airways and lung tissue and development of an goblet cell metaplasia), cell and molecular biological methods will be performed to identify the effector mechanism of VacA in vivo.Aim 2: Analysis of the immunoregulatory influence of VacA on DC and their interaction with T cells. Impact of VacA on DC activation, allergen uptake and processing will be analyzed in detail using cell and molecular biological assays and gene expression analysis. Moreover, it will be analyzed how VacA affects the allergen-specific and –unspecific interaction between DC and T cells. The analyses will be performed with murin and human experimental setups to draw conclusions about the effectiveness of a VacA treatment in humans.Aim 3: Using a humanized mouse model of allergic airway disease will be further confirm the therapeutic impact of an VacA application on human cells under in vivo conditions.

• DFG Programme: Research Grants