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Development of a Glycocluster Adjuvant Mimicking Natural Yeast beta-(1,2)-Structures

Mäkinen, Kaarina (2015-01-16)

dc.contributorDepartment of Clinical Medicine, Pulmonary Diseases and Clinical Allergology-
dc.contributor.authorMäkinen, Kaarina
dc.date.accessioned2014-12-23T05:46:26Z
dc.date.available2014-12-23T05:46:26Z
dc.date.issued2015-01-16
dc.identifierISBN 978-951-29-5942-6-
dc.identifier.urihttp://www.utupub.fi/handle/10024/103051
dc.description.abstractAllergy is characterized by T helper (Th) 2-type immune response after encounter with an allergen leading to subsequent immunoglobulin (Ig) E-mediated hypersensitivity reaction and further allergic inflammation. Allergen-specific immunotherapy (SIT) balances the Th2-biased immunity towards Th1 and T regulatory responses. Adjuvants are used in allergen preparations to intensify and modify SIT. β-(1,2)-oligomannoside constituents present in Candida albicans (C. albicans) cell wall possess Th1-type immunostimulatory properties. The aim of this thesis was to develop a β-(1,2)-linked carbohydrate compound with known structure and anti-allergic properties to be applied as an adjuvant in SIT. First the immunostimulatory properties of various fungal extracts were studied. C. albicans appeared to be the most promising Th1-inducing extract, which led to the synthesis of various mono- or divalent oligomannosides designed on the basis of C. albicans. These carbohydrates did not induce strong cytokine production in human peripheral blood mononuclear cell (PBMC) cultures. In contrast to earlier reports using native oligosaccharides from C. albicans, synthetic -(1,2)-linked mannotetraose did not induce any tumor necrosis factor production in murine macrophages. Next, similarities with synthesized divalent mannosides and the antigenic epitopes of β-(1,2)-linked C. albicans mannan were investigated. Two divalent compounds inhibited specific IgG antibodies binding to below 3 kDa hydrolyzed mannan down to the level of 30–50% showing similar antigenicity to C. albicans. Immunomodulatory properties of synthesized carbohydrate assemblies ranging from mono- to pentavalent were evaluated. A trivalent acetylated dimannose (TADM) induced interleukin-10 (IL-10) and interferon-γ responses. TADM also suppressed birch pollen induced IL-4 and IL-5 responses in allergen (Bet v) stimulated PBMCs of birch pollen allergic subjects. This suppression was stronger with TADM than with other used adjuvants, immunostimulatory oligonucleotides and monophosphoryl lipid A. In a murine model of asthma, the allergen induced inflammatory responses could also be suppressed by TADM on cytokine and antibody levels.-
dc.language.isoeng-
dc.publisherAnnales Universitatis Turkuensis D 1148-
dc.publisherfi=Turun yliopisto|en=University of Turku|en
dc.relation.ispartofseriesTurun yliopiston julkaisuja. Sarja D, Medica – Odontologica
dc.titleDevelopment of a Glycocluster Adjuvant Mimicking Natural Yeast beta-(1,2)-Structures-
dc.type.ontasotfi=Artikkeliväitöskirja|en=Doctoral dissertation (article-based)|
dc.identifier.urnURN:ISBN:978-951-29-5942-6-
dc.relation.issn2343-3213
dc.description.notificationSiirretty Doriasta
dc.contributor.facultyfi=Lääketieteellinen tiedekunta|en=Faculty of Medicine|
dc.contributor.departmentfi=Kliininen laitos|en=Institute of Clinical Medicine|
dc.format.contentfulltext
dc.relation.numberinseries1148-
dc.description.accessibilityfeatureei tietoa saavutettavuudesta


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