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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.