Investigating the potential of bacillus calmette-guerin vaccine russia strain, cpg oligonucleotides and intravenous immunoglobulin to induce trained immunity in the context of antiviral immunity

Baydemir, İlayda
Innate immune cells undergo metabolic and epigenetic reprogramming in response to specific stimuli, that enable a more robust immune response to secondary exposure to a wide variety of pathogens. This process of innate immune memory development has been termed as Trained Immunity (TI). BCG vaccine is one well-known inducer of innate immune memory. In vivo administration of CpG ODNs or Intravenous Immunoglobulin (IVIg) can also exert heterologous anti-microbial protective immunity. In this thesis, we sought to evaluate the potential of BCG vaccine (Russia strain), CpG ODNs and IVIg to induce trained immunity in hPBMCs particularly in the context of activating antiviral immune responses through assessment of intracellular ISG15 levels, APC activation and cytokine/chemokine production in response to secondary virus mimetic ligand stimulation. Our findings showed that BCG vaccine, CpG ODNs and IVIg could re-program hPBMCs in vitro and increase their responsiveness to a secondary stimulation with viral ligands. vi To confirm our in vitro findings regarding BCG-induced trained immunity, we examined the effects of BCG vaccine on the antiviral immune responses of 9 healthy volunteers prior to and 4 weeks after vaccination at protein and mRNA levels. BCG vaccination increased only TLR3-mediated intracellular ISG15 levels, enhanced APC maturation as well as IP-10 and IL-1β production following various secondary viral and/or bacterial ligand stimulations. Moreover, BCG vaccine improved the mobilization of myeloid progenitor-derived cells from bone marrow. Gene expression analysis also confirmed the functional/phenotypic alterations caused by BCG-induced trained immunity at mRNA level, suggesting that BCG vaccination can increase recall responses of individuals to a potential secondary viral infection.


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Geçkin, Büşranur; Gürsel, Mayda; Department of Biology (2019)
Intravenous Immunoglobulin (IVIg) is mainly composed of IgG derived from pooled plasma of healthy individuals and used to treat variety of immune diseases. Low dose administration can activate the immune system in case of immunodeficiencies, while high doses suppress immune responses in autoimmune/autoinflammatory conditions. The mechanisms underlying this disparate effect is poorly understood. Herein, we examined the effects of IVIg treatment on the functionality of specific innate immune cell populations ...
Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG
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Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized by the cytosolic DNA sensor STING (stimulator of IFN genes), initiating a response characterized by proinflammatory cytokine and type I IFN production. Strategies to improve the immune stimulatory activities of CDNs can further their potential for clinical development. Here, we demonstrat...
Immunotherapeutic utility of stimulatory and suppressive oligodeoxynucleotides.
Ishii, KJ; Gursel, I; Gürsel, Mayda; Klinman, DM (2004-04-01)
Bacterial DNA contains immunostimulatory CpG motifs that interact with toll-like receptor 9 on immune cells to stimulate the production of cytokines, chemokines and immunoglobulins. Synthetic oligodeoxynucleotides (ODNs) containing CpG motifs mimic the activity of bacterial DNA. Recently, several structurally distinct types of CpG ODN were identified that differentially activate human immune cells. These ODNs may be useful as vaccine adjuvants, anti-allergens and in the treatment of infectious diseases and ...
Evaluating Oxygen Tensions Related to Bone Marrow and Matrix for MSC Differentiation in 2D and 3D Biomimetic Lamellar Scaffolds
Sayin, Esen; Baran, Erkan Turker; Elsheikh, Ahmed; Mudera, Vivek; Cheema, Umber; Hasırcı, Vasıf Nejat (2021-04-01)
The physiological O-2 microenvironment of mesenchymal stem cells (MSCs) and osteoblasts and the dimensionality of a substrate are known to be important in regulating cell phenotype and function. By providing the physiologically normoxic environments of bone marrow (5%) and matrix (12%), we assessed their potential to maintain stemness, induce osteogenic differentiation, and enhance the material properties in the micropatterned collagen/silk fibroin scaffolds that were produced in 2D or 3D. Expression of ost...
Characterization of extracellular beta-lactamases from penicillin G-resistant cells of Streptococcus thermophilus
Chirica, LC; Güray, Nülüfer Tülün; Gültekin, Güzin Candan; Bozoglu, F (International Association for Food Protection, 1998-07-01)
In this study, biochemical properties of two extracellular beta-lactamases produced by penicillin-resistant Streptococcus thermophilus cells were investigated. Both beta-lactamases showed specificity for penicillins but not for cephaloridins. The p-lactamases exhibited different affinities for penicillin G. The one with the higher molecular weight (F1) had a K(m) value of 3.44 mu M and a V(max), value of 8.33, mu mol/min/mg of protein, whereas the beta-lactamase with the lower molecular weight (FII) had a K...
Citation Formats
İ. Baydemir, “Investigating the potential of bacillus calmette-guerin vaccine russia strain, cpg oligonucleotides and intravenous immunoglobulin to induce trained immunity in the context of antiviral immunity,” M.S. - Master of Science, Middle East Technical University, 2020.