Targeting adenosine receptors to improve vaccine efficacy

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buir.advisorÇekiç, Çağlar
dc.contributor.authorSavaş, Ali Can
dc.date.accessioned2017-01-13T10:21:24Z
dc.date.available2017-01-13T10:21:24Z
dc.date.copyright2016-12
dc.date.issued2016-12
dc.date.submitted2017-01-09
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2016.en_US
dc.descriptionIncludes bibliographical references (leaves 74-82).en_US
dc.description.abstractVaccination is the major protection method against many diseases caused by pathogens through creating acquired immunity. Vaccines can be classified in two major groups, which are subunit vaccines and attenuated vaccines. Attenuated vaccines can create effective immunity however; they also can induce many different side effects such as fever and allergic reactions. On the contrary, with subunit vaccines side effects are decreased but the efficacy of the vaccines is also decreased and there is a need for repetitive vaccinations to provide long lasting immunity. That is why, there is a need for developing more efficient vaccines and particularly vaccine adjuvants. Adenosine receptors, as part of purinergic signaling, have a regulatory role in immune system. Adenosine and 4 different adenosine receptors have an immunosuppressive role in major immune cells to create acquired immunity such as DCs, macrophages and lymphocytes. That is why, we hypothesize that, the efficacy of vaccines can be decreased by endogenous adenosine and the usage of antagonists in adjuvant formulations can increase this efficacy by inhibiting the suppressive effects caused by endogenous adenosine. To be able to test this hypothesis, we first determine the specific adenosine receptor and antagonists taking a role in this immunosuppressive effect. For this purpose, we use primary dendritic cells and macrophages. We see that A2A and A2B receptors create most effective immunosuppression and SCH 58261 (A2A antagonist) and PSB 603 (A2B antagonist) are the main antagonists taking a role in the inhibition of this suppression. We then evaluated these two molecules in a vaccine formulation comprising MPL-A and AddaVax. As a result, these antagonists do not significantly change the general initial immune responses significantly however they create more antigen specific response. On the other hand, after antigen re-stimulation, mice taking these antagonists shows more antigen specific response and they also create higher antibody titers. With this study, adenosine receptor antagonists used in adjuvant formulations for the first time and it was shown that, with more study, they can be important in increasing vaccine efficacy created by immunostimulatory adjuvants.en_US
dc.description.degreeM.S.en_US
dc.description.statementofresponsibilityby Ali Can Savaş.en_US
dc.embargo.release2019-01-09
dc.format.extentxvii, 93 leaves : charts (some color)en_US
dc.identifier.itemidB153024
dc.identifier.urihttp://hdl.handle.net/11693/32608
dc.language.isoEnglishen_US
dc.publisherBilkent Universityen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAdenosineen_US
dc.subjectAdenosine Receptorsen_US
dc.subjectVaccinesen_US
dc.subjectAdjuvantsen_US
dc.titleTargeting adenosine receptors to improve vaccine efficacyen_US
dc.title.alternativeAdenozin almaçlarının hedeflenerek aşı etkinliğinin arttırılmasıen_US
dc.typeThesisen_US

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Dept. of Molecular Biology and Genetics - Master's degree