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Pulmonary immune responses to bio-mimetic antigen carriers for novel therapeutic approaches to treating allergic asthma

English title Pulmonary immune responses to bio-mimetic antigen carriers for novel therapeutic approaches to treating allergic asthma
Applicant von Garnier Christophe
Number 146249
Funding scheme Project funding
Research institution Universitätsklinik für Pneumologie Inselspital
Institution of higher education University of Berne - BE
Main discipline Immunology, Immunopathology
Start/End 01.08.2013 - 31.10.2016
Approved amount 343'960.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Cellular Biology, Cytology

Keywords (9)

astma; dendritic cell; liposome; virosome; immunology; macrophage; particle; allergy; respiratory tract

Lay Summary (German)

Lead
Trotz Forschung auf dem Gebiet von bio-mimetischen Antigenträgern (Partikel im Nano- und Micrometerbereich, Virosome und Liposome) in der Medizin ist wenig über deren immunologische Wirkung bekannt. Weltweit leiden 235 Mio Menschen an Asthma bronchiale und in der Hälfte spielt eine Allergie eine Rolle. Die Lunge ist mit ihrer grossen Oberfläche und einem effizienten Immunsystem ein attraktives Zielorgan für neuartige immunmodulatorische Therapieansätze mit bio-mimetischen Antigenträgern.
Lay summary

Inhalt und Ziel des Forschungsprojekts
Unser übergeordnetes Ziel ist es, die Wirkung verschiedener Antigenträger auf Immunzellen und auf die Immunantwort in den Atemwegen zu klären. Insbesondere soll das Potenzial bio-mimetischer Antigenträger als zukünftige, neuartige Behandlungstrategie bei allergischem Asthma bronchiale untersucht werden. In einem Model für allergisches Asthma bronchiale soll die Wirkung bio-mimetischer Antigenträger auf dendritische Zellen und Makrophagen in den Atemwegen, sowie die Anpassung der Immunantwort erforscht werden.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts
Unser multidisziplinären Projekt soll zu einer verbesserten translationellen Forschung für immunmodulatorische Therapiestrategien bei allergischem Asthma bronchiale führen. Damit soll unser Verständnis für die Auswirkung verschiedener bio-mimetischer Antigenträger auf die Atemwege verbessert werden und einen Beitrag für verbesserte zukünftige Impf- und Therapiestrategien über die Lunge geliefert werden. Dies ist wichtig, um einer ausgeprägt emotionalen öffentlichen Debatte über mögliche gesundheitliche Auswirkungen von zukünftigen medizinischen Anwendungen mit Partikeln im Nanometerbereich mit möglichst objektiven Daten zu begegnen.

Direct link to Lay Summary Last update: 29.07.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Virosome-bound antigen enhances DC-dependent specific CD4+ T cell stimulation, inducing a Th1 and Treg profile in vitro
Blom Rebecca A.M., Amacker Mario, Moser Christian, van Dijk R. Maarten, Bonetti Raffaela, Seydoux Emilie, Hall Sean R.R., von Garnier Christophe, Blank Fabian (2017), Virosome-bound antigen enhances DC-dependent specific CD4+ T cell stimulation, inducing a Th1 and Treg profile in vitro, in Nanomedicine: Nanotechnology, Biology and Medicine, 13(5), 1725-1737.
Pulmonary Delivery of Virosome-Bound Antigen Enhances Antigen-Specific CD4+ T Cell Proliferation Compared to Liposome-Bound or Soluble Antigen
Blom Rebecca A. M., Amacker Mario, van Dijk R. Maarten, Moser Christian, Stumbles Philip A., Blank Fabian, von Garnier Christophe (2017), Pulmonary Delivery of Virosome-Bound Antigen Enhances Antigen-Specific CD4+ T Cell Proliferation Compared to Liposome-Bound or Soluble Antigen, in Frontiers in Immunology, 8, 1.
A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes
Blom Rebecca A. M., Erni Silvia T., Krempaská Kristína, Schaerer Olivier, van Dijk R. Maarten, Amacker Mario, Moser Christian, Hall Sean R. R., von Garnier Christophe, Blank Fabian (2016), A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes, in PLOS ONE, 11(9), e0163539-e0163539.
A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes.
Blom RA (2016), A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes., in PLoS One, e0163539.

Collaboration

Group / person Country
Types of collaboration
Prof Phil Stumbles Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr Mario Amacker Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
Dr. Christian Moser Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
International Congress of Cell Biology Talk given at a conference Particle surface composition modulates the pulmonary immune response 21.07.2016 Prague, Czech Republic Blom Rebecca; von Garnier Christophe;
Annual Meeting Swiss Society for Pulmonology Talk given at a conference Virosomes coupled to antigen induce enhanced specific cd4+ t cell activation compared to liposomes in an in vitro model of pulmonary dendritic cells 15.06.2016 Lausanne, Switzerland von Garnier Christophe; Blom Rebecca;
European Academy of Allergy and Clinical Immunology Poster Virosomes show faster uptake dynamics and a stronger activating potential than liposomes in an in vitro model of pulmonary dendritic cells 06.06.2015 Barcelona, Spain von Garnier Christophe; Blom Rebecca;
Annual Meeting Swiss Society for Pulmonology Talk given at a conference Virosomes and Liposomes Show Different Uptake Dynamics and Activating Potential in Dendritic Cells 16.04.2015 Lugano, Switzerland Blom Rebecca; von Garnier Christophe;
European Respiratory Society Lung Science Conference Poster Interaction between dendritic cells and bio-mimetic antigen carriers to modulate specific immune responses in the respiratory tract 13.03.2015 Estoril, Portugal von Garnier Christophe; Blom Rebecca;
Annual Meeting Swiss Society for Pulmonology Talk given at a conference Interaction between dendritic cells and bio-mimetic antigen carriers to modulate specific immune responses in the respiratory tract 08.05.2014 Interlaken, Switzerland von Garnier Christophe; Blom Rebecca;


Awards

Title Year
Abstract Prize Winner European Academy of Allergy and Clinical Immunology, Barcelona (Spain) 2015
Department of Clinical Research Travel Grant, Bern (Switzerland) 2015
Graduate School for Cellular and Biomedical Sciences Travel Grant, Bern (Switzerland) 2015

Associated projects

Number Title Start Funding scheme
157748 Microscopy Equipment for Organ-on-Chips and Perfused Microfluidic Systems with High Speed Camera 01.12.2014 R'EQUIP
120161 Development of a Nanoparticle Library for Comprehensive Investigation of the Particle behaviour under Physiological Conditions 01.10.2008 Project funding
131266 Biomedical nanoparticles as immune-modulators 01.05.2011 NRP 64 Opportunities and Risks of Nanomaterials
122355 Pulmonary immune responses to biomedical nanoparticles and therapeutical applications 01.03.2009 Project funding
141875 Dysregulation of the Lung Microbiota in Chronic Obstructive Pulmonary Disease 01.11.2012 Sinergia
159847 Towards a fundamental understanding of nanoparticle exocytosis from cells 01.10.2015 Project funding

Abstract

Over the last decade there has been intensive research in the area of bio-mimetic carrier systems, notably for synthetic particles in the nanometer and micrometer range, virosomes, and liposomes. Despite some compounds being utilised in clinical applications, our knowledge regarding immune responses related to such particulates remains incomplete. This lack in our understanding and concerns arising from effects of ambient combustion-derived particles and the fragile gas exchange barrier, has excluded to date development of such carrier systems for the pulmonary route of administration. Yet, with its vast surface area and tightly enmeshed network of dendritic cells and macrophages, the respiratory tract represents an ideal target organ for immune-modulation. Asthma is a major non-communicable disease with an estimated 235 Million individuals suffering from this chronic debilitating disorder and its rates rising worldwide. In about half of the asthmatic individuals, an allergic component with a skewed immune response to an innocuous antigen constitutes a relevant trigger and perpetuator that ultimately influences the course and prognosis of this disease. Our hypothesis is that bio-mimetic antigen carriers (synthetic biomedical particles, virosomes, liposomes) delivered to antigen-presenting cells (dendritic cells, macrophages) in the respiratory tract modulate adaptive immune responses and represent a novel approach to treating allergic airways disease.In our proposal we aim to employ a multi-disciplinary approach to discover how bio-mimetic antigen carriers interact with different antigen-presenting cells in the respiratory tract and modulate down-stream immune responses. Parallel in vitro and in vivo comparisons of different bio-mimetic carriers will be initiated with the goal of providing some of the first in field data to reveal how their specific characteristics will determine uptake by dendritic cells and macrophages, trafficking to lymph nodes, and modulation of T cell responses in a murine model of allergic airways disease.
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