Farklı Tipteki Aluminyum Adjuvanların Monositik Hücrelerde Oluşturduğu Etkilerin Proteomiks ve Metabolomiks Düzeyde İncelenmesi

Abstract

Kabakoğlu, F., Investigation of The Effects of Aluminium Adjuvants on Monocytic Cells at The Proteomics and Metabolomics Level. Hacettepe University, Hacettepe University Health Sciences Institute, Vaccine Studies Program, Master Thesis, Ankara, 2023. Vaccines are biological compounds that reduce the mortality and morbidity of diseases caused by infectious diseases by mimicking natural infection and producing long-term immunological memory. Since most of the antigens used in vaccines cause weak immunological response, adjuvants are also added to the vaccine components in order to increase the potency and duration of the effect of the vaccines. Since ancient times, aluminum salts have been the most commonly used adjuvants and provide a particularly strong stimulus to monocytes to differentiate into a mature dendritic phenotype. In this thesis, metabolomics and proteomics studies were carried out using different concentrations of aluminum oxyhydroxide (AH) and aluminum hydroxyphosphate (AP) salts in U-937 and THP-1 cell cultures. For this purpose, intracellular and extracellular metabolomics analyzes with gas chromatography-mass spectrometry (GC-MS) and proteomics analyzes were performed with liquid chromatography-cyclopol time-of-flight mass spectrometry (LC-qTOF-MS). As a result of the analysis, a total of 170 metabolites and 403 proteins were identified. Univariate and multivariate data analyzes allowed the identification of metabolites, proteins and pathways that vary depending on aluminum adjuvant salts and THP-1 and U937 cell culture types. It is thought that endogenic metabolites and proteins that change significantly in cells exposed to different concentrations of AH and AP salts may lead to the strengthening of the effect of existing aluminum adjuvants and the development of new endogenous adjuvants.