Browsing by Author "Demircan, Muhammed Burak"

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Open Access
Biotin functionalized self‐assembled peptide nanofiber as an adjuvant for immunomodulatory response
(Wiley-VCH Verlag, 2020-12) Demircan, Muhammed Burak; Tohumeken, Sehmus; Gündüz, Nuray; Khalily, Mohammad Aref; Tekinay, T.; Güler, M. O.; Tekinay, Ayşe B.
Biotinylated peptide amphiphile (Biotin‐PA) nanofibers, are designed as a noncovalent binding location for antigens, which are adjuvants to enhance, accelerate, and prolong the immune response triggered by antigens. Presenting antigens on synthetic Biotin‐PA nanofibers generated a higher immune response than the free antigens delivered with a cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODN) (TLR9 agonist) adjuvant. Antigen attached Biotin‐PA nanofibers trigger splenocytes to produce high levels of cytokines (IFN‐γ, IL‐12, TNF‐α, and IL‐6) and to exhibit a superior cross‐presentation of the antigen. Both Biotin‐PA nanofibers and CpG ODN induce a Th‐1‐biased IgG subclass response; however, delivering the antigen with Biotin‐PA nanofibers induce significantly greater production of total IgG and subclasses of IgG compared to delivering the antigen with CpG ODN. Contrary to CpG ODN, Biotin‐PA nanofibers also enhance antigen‐specific splenocyte proliferation and increase the proportion of the antigen‐specific CD8(+) T cells. Given their biodegradability and biocompatibility, Biotin‐PA nanofibers have a significant potential in immunoengineering applications as a biomaterial for the delivery of a diverse set of antigens derived from intracellular pathogens, emerging viral diseases such as COVID‐19, or cancer cells to induce humoral and cellular immune responses against the antigens.
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Çernobil nükleer faciasının insan yaşamı ve çevre üzerindeki etkileri
(Bilkent University, 2012) Sarıoğuz, Tolga; Dinç, Alper Buğra; Karakaş, Güllü; Demircan, Muhammed Burak
Open Access
A self assembled nanofibrous structure as a novel vaccine adjuvant
(2017-01) Demircan, Muhammed Burak
Vaccination is the most effective and cost-efficient way of protection against the major infectious diseases but ideal vaccine formulation has not been found. Recent vaccine systems are mainly composed of two major substitutes that are antigen and adjuvant. Recently it was demonstrated that widely used adjuvants exhibit some safety problems that affect the neural system such as neurotoxicity and autoimmune diseases. Therefore, there are increased concerns about side effects of the adjuvants and many researchers focus on developing new adjuvants that are effective and safe. Peptide amphiphiles are chemically defined molecules that are able to self-assemble into nanofibrous structures. The nanofibrous structures are biocompatible, biodegradable, and biosafe and thereby they are ideal for vaccine systems. Also, nanofibrous structures don’t contain any substance that are potentially dangerous for neural system such as metals. Thus, nanofibrous structures are promising candidates to be alternative novel vaccine adjuvants. In this thesis, I investigated the potential of a biotinylated nanofibrous structure as a novel vaccine adjuvant that is potentially safe. Briefly, biotinylated peptide amphiphiles were synthesized, purified and characterized to analyze the features of the novel material. The peptide amphiphiles were induced to form nanofibrous structures by self-assembly and antigens (ovalbumin) were bound to the biotinylated nanofibrous structures through streptavidin linkers. Splenocytes were treated with the nanofibrous structures to demonstrate the effects of the nanofibrous structures on the immune response. After the confirmation of efficient immune response that are induced by the nanofibrous structure in vitro, as enhancing release of stimulatory cytokines, inducing dendritic cell maturation and triggering the cross-presentation of the antigen, mice were immunized with the nanofibrous structure in the presence of antigen for further analysis of the nanofibrous structure efficiency as adjuvant in vivo. Both in vivo and in vitro results showed that the nanofibrous structure is able to effectively trigger the antigen specific immune response and thereby exhibit adjuvant properties. Overall, I suggest that the nanofibrous structure is able to be used as a new vaccine adjuvant that induces effective antigen specific adoptive immune response and thereby it could be a good alternative of recently used adjuvants that are suspected to contribute some impairments in neural system.