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Characterization of IgY for Oral Immunotherapy and Prevention of Pseudomonas aeruginosa Infections in Cystic Fibrosis Patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chicken antibodies, commonly referred to as IgY, have several properties that make them suitable for oral treatment of infections and there is essentially no risk for development of resistance. The overall aims of this thesis were to investigate Anti-Pseudomonas IgY as prophylaxis against infections with Pseudomonas aeruginosa for cystic fibrosis (CF) patients and to characterize the antibody treatment.

We found that Anti-Pseudomonas IgY has affinity for P. aeruginosa flagellin, the major component of the flagellum. This is important since the flagellum is required for host invasion and establishment of infection. Flagellin induces inflammation.

The main cause of morbidity and mortality among CF patients is chronic colonization of the airways with P. aeruginosa. We have studied prophylactic treatment of 17 Swedish CF patients with Anti-Pseudomonas IgY for up to twelve years. The results were compared with a control group of 23 Danish CF patients. Patients treated with IgY had 2.3 P. aeruginosa positive cultures/100 treatment months vs. 7.0 cultures/100 treatment months in the control group (p=0.028), and the time from inclusion to the first recolonization was significantly longer in the IgY-treated group (p=0.012). Lung function was preserved and patients treated with IgY had good nutritional status at the end of the study. Furthermore, other bacteria have not emerged instead of P. aeruginosa.

Freeze-drying of IgY and the content of IgY preparations for oral use was investigated. Besides IgY, 26 egg yolk proteins were identified. Some of the proteins are known to have antimicrobial and immunostimulatory effects, and could have a positive additive effect to IgY treatment. Cholesterol levels were low.

Conclusion: Anti-Pseudomonas IgY is a promising complement in the prevention of Pseudomonas aeruginosa infections in CF patients, partly explained by the fact that IgY binds to flagellin.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2009. , p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 442
National Category
Other Clinical Medicine
Research subject
Clinical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-100191ISBN: 978-91-554-7478-2 (print)OAI: oai:DiVA.org:uu-100191DiVA, id: diva2:209709
Public defence
2009-05-08, Enghoffsalen, ing. 50, Akademiska sjukhuset, Uppsala, 09:15 (English)
Opponent
Supervisors
Note
Felatkigt ISBN ändrat: Tidigare 978-91-554-7477-5 nu 978-91-554-7478-2 Available from: 2009-04-17 Created: 2009-03-26 Last updated: 2009-06-02Bibliographically approved
List of papers
1. Stability of chicken IgY antibodies freeze-dried in the presence of lactose, sucrose and trehalose
Open this publication in new window or tab >>Stability of chicken IgY antibodies freeze-dried in the presence of lactose, sucrose and trehalose
2007 (English)In: Journal of Poultry Science, ISSN 1349-0486, Vol. 44, no 1, p. 58-62Article in journal (Refereed) Published
Abstract [en]

Freeze-drying is used as a method to stabilize proteins. The process itself may however cause protein unfolding and denaturation, but the risk is reduced if a stabilizing agent is added prior to freeze-drying. Here chicken antibody (IgY) preparations were freeze-dried in the presence or absence of lactose, sucrose and threalose as stabilizing agent at 0.3, 0.06 and 0.012M. The activity of freeze-dried IgY batches in the absence of stabilizing agent was similar before and after freeze-drying, but decreased slowly during eight weeks at 37°C. Addition of disaccharide resulted in a preserved activity after eight weeks in 37°C, compared to samples with no sugar added. The results were similar irrespective of sugar type and concentration (0.012-0.3M). This shows that IgY freeze-dried in the presence of disaccharide is very stable and a method to reduce the cost and simplify transport, storage and use of avian antibodies.

Keywords
ELISA, freeze-drying, IgY, lactose, sucrose, threalose
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-12980 (URN)
Available from: 2008-01-19 Created: 2008-01-19 Last updated: 2010-04-09Bibliographically approved
2.
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3. Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin: Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin
Open this publication in new window or tab >>Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin: Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin
2007 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 856, no 1-2, p. 75-80Article in journal (Refereed) Published
Abstract [en]

Pseudomonas aeruginosa (PA) is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. CF patients with chronic PA infections have a more rapid deterioration of their lung function and the bacteria become impossible to eradicate from the lungs. Antibiotic resistance among PA strains in CF patients is steadily increasing. Specific chicken (IgY) antibodies against PA have been shown to have potential to prevent PA infections in CF. Anti-Pseudomonas IgY reduces PA adhesion to epithelia, but the mechanism has not been fully elucidated. To gain further insight into the prophylactic effect of these antibodies, the immunoreactivity was investigated by 2D electrophoresis of PA strains, immunoblotting and MALDI-TOF-MS. To confirm the identity of the proteins, the tryptic peptides were analyzed by MALDI-TOF-MS to accurately measure their monoisotopic masses as well as determine their amino acid sequences. In order to facilitate fragmentation of the peptides they were N-terminally or C-terminally labeled. Several strains were investigated and anti-Pseudomonas IgY was immunoreactive against all of these strains, which strengthens its potential as a prophylactic treatment against PA. Flagellin was identified as the major antigen. Flagellin is the main protein of the flagella and is crucial for establishing infections in hosts as well as being involved in PA chemotaxis, motility, adhesion and inflammation. Furthermore, secreted flagellin elicits an inflammatory response. In conclusion, anti-Pseudomonas IgY binds flagellin, which may prevent PA infections in CF patients by hindering host invasion.

Keywords
two-dimensional gel electrophoresis, antigen, IgY, mass spectrometry, proteomics
National Category
Medical and Health Sciences Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-100189 (URN)10.1016/j.jchromb.2007.05.029 (DOI)000249615100012 ()17581799 (PubMedID)
Available from: 2009-03-26 Created: 2009-03-26 Last updated: 2017-12-13Bibliographically approved
4.
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