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  1. Article ; Online: Immunogenicity and Protective Capacity of CpG ODN Adjuvanted Alum Adsorbed Bivalent Meningococcal Outer Membrane Vesicle Vaccine.

    Canavar Yildirim, Tugce / Ozsurekci, Yasemin / Yildirim, Muzaffer / Evcili, Irem / Yazar, Volkan / Aykac, Kubra / Guler, Ulku / Salih, Bekir / Gursel, Mayda / Gursel, Ihsan

    International immunology

    2024  

    Abstract: Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N.meningitidis have been developed albeit with a short-lived ... ...

    Abstract Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N.meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal assays (SBA) based protective coverage of OMV vaccine to X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W+B OMV vaccine, either adjuvanted with Alum, CpG ODN or their combinations and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer) and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through ELISA and SBA. Antibody responses and SBA titers were significantly higher in the W+B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W+B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W+B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines.
    Language English
    Publishing date 2024-03-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 1013745-2
    ISSN 1460-2377 ; 0953-8178
    ISSN (online) 1460-2377
    ISSN 0953-8178
    DOI 10.1093/intimm/dxae016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2619: Show issues Location:
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  2. Article ; Online: The role of bcsE gene in the pathogenicity of Salmonella.

    Özdemir, Caner / Akçelik, Nefise / Neslihan Özdemir, Fatma / Evcili, İrem / Kahraman, Tamer / Gürsel, İhsan / Akçelik, Mustafa

    Pathogens and disease

    2021  Volume 79, Issue 6

    Abstract: The effects of the bcsE gene and BcsE protein on bacterial physiology and pathogenicity in SalmonellaTyphimurium and Salmonella Group C1 were investigated. It was observed that biofilm and pellicle formation did not occur in the bcsE gene mutants of wild- ...

    Abstract The effects of the bcsE gene and BcsE protein on bacterial physiology and pathogenicity in SalmonellaTyphimurium and Salmonella Group C1 were investigated. It was observed that biofilm and pellicle formation did not occur in the bcsE gene mutants of wild-type strains. Besides, the 'rdar' (red, dry, rough) biofilm morphotype in wild-type strains changed significantly in the mutants. In terms of the bcsE gene, the swimming and swarming motility in mutant strains showed a dramatic increase compared to the wild-type strains. The Salmonella bcsE gene was cloned into Escherichia coli BL21, and the his-tagged protein produced in this strain was purified to obtain polyclonal antibodies in BALB/c mice. The antibodies were showed labeled antigen specificity to the BscE protein. As a result of immunization and systemic persistence tests carried out with BALB/c mice, BscE protein was determined to trigger high levels of humoral and cellular responses (Th1 cytokine production, IgG2a/IgG1 > 1). Systemic persistence in the liver and spleen samples decreased by 99.99% and 100% in the bcsE mutant strains. Finally, invasion abilities on HT-29 epithelial cells of wild-type strains were utterly disappeared in their bcsE gene mutant strains.
    MeSH term(s) Animals ; Bacterial Proteins/physiology ; Biofilms ; Cloning, Molecular ; DNA, Bacterial ; Escherichia coli/genetics ; HT29 Cells ; Humans ; Membrane Proteins/physiology ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; Recombinant Proteins/metabolism ; Salmonella/pathogenicity ; Salmonella/physiology ; Salmonella Infections/immunology ; Salmonella Infections/microbiology ; Sequence Deletion ; Virulence
    Chemical Substances Bacterial Proteins ; DNA, Bacterial ; Membrane Proteins ; Recombinant Proteins
    Language English
    Publishing date 2021-07-19
    Publishing country United States
    Document type Journal Article
    ISSN 2049-632X
    ISSN (online) 2049-632X
    DOI 10.1093/femspd/ftab037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: TLR ligand loaded exosome mediated immunotherapy of established mammary Tumor in mice.

    Yildirim, Muzaffer / Yildirim, Tugce Canavar / Turay, Nilsu / Bildik, Tugce / Ibibik, Bilgehan / Evcili, Irem / Ersan, Pelin Gulizar / Tokat, Unal M / Sahin, Ozgur / Gursel, Ihsan

    Immunology letters

    2021  Volume 239, Page(s) 32–41

    Abstract: Tumor-derived exosomes (TEXs) could be harnessed as an immunotherapeutic cancer vaccine. These nanovesicles are inherently possesses rich tumor antigen reservoirs. Due to their undesirable features such as poor or limited immunogenicity as well as ... ...

    Abstract Tumor-derived exosomes (TEXs) could be harnessed as an immunotherapeutic cancer vaccine. These nanovesicles are inherently possesses rich tumor antigen reservoirs. Due to their undesirable features such as poor or limited immunogenicity as well as facilitation of cancer development via mediating communication between tumor cells TEXs could be transformed into an effective immune adjuvant delivery system that initiates a strong humoral and cell-mediated tumor-specific immune response. Engineering TEXs to harbor immunostimulatory molecules still remains a challenge. Previously, we demonstrated that nucleic acid ligand encapsulated liposomes could trigger synergistic strong humoral, and cell mediated immune responses and provokes tumor regression to that of their standalone counterparts. In this study, we evaluated to immunogenicity of 4T1/Her2 cell-derived exosomes upon loading them with two potent immuno adjuvant, a TLR9 ligand, K-type CpG ODN and a TLR3 ligand, p(I:C). Engineered TEXs co-encapsulating both ligands displayed boosted immunostimulatory properties by activating antigen-specific primary and memory T cell responses. Furthermore, our exosome-based vaccine candidate elicited robust Th1-biased immunity as evidenced by elevated secretion of IgG2a and IFNγ. In a therapeutic cancer model, administration of4T1 tumor derived exosomes loaded with CpG ODN and p(I:C) to animals regress tumor growth in 4T1 tumor-bearing mice. Taken together this work implicated that an exosome-based therapeutic vaccine promoted strong cellular and humoral anti-tumor immunity that is sufficient to reverse established tumors. This approach offers a personalized tumor therapy strategy that could be implemented in the clinic.
    Language English
    Publishing date 2021-08-18
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 445150-8
    ISSN 1879-0542 ; 0165-2478
    ISSN (online) 1879-0542
    ISSN 0165-2478
    DOI 10.1016/j.imlet.2021.08.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection.

    Yilmaz, Ismail Cem / Ipekoglu, Emre Mert / Bulbul, Artun / Turay, Nilsu / Yildirim, Muzaffer / Evcili, Irem / Yilmaz, Naz Surucu / Guvencli, Nese / Aydin, Yagmur / Gungor, Bilgi / Saraydar, Berfu / Bartan, Asli Gulce / Ibibik, Bilgehan / Bildik, Tugce / Baydemir, İlayda / Sanli, Hatice Asena / Kayaoglu, Basak / Ceylan, Yasemin / Yildirim, Tugce /
    Abras, Irem / Ayanoglu, Ihsan Cihan / Cam, Sefa Burak / Ciftci Dede, Eda / Gizer, Merve / Erganis, Osman / Sarac, Fahriye / Uzar, Serdar / Enul, Hakan / Adiay, Cumhur / Aykut, Gamze / Polat, Hivda / Yildirim, Ismail Selim / Tekin, Saban / Korukluoglu, Gulay / Zeytin, Hasan Ersin / Korkusuz, Petek / Gursel, Ihsan / Gursel, Mayda

    Allergy

    2021  Volume 77, Issue 1, Page(s) 258–270

    Abstract: Background: Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the ... ...

    Abstract Background: Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the four structural proteins of SARS-CoV-2.
    Methods: VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable-resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine.
    Results: Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS-CoV-2. Alum adsorbed, K3-CpG ODN-adjuvanted VLPs elicited high titer anti-S, anti-RBD, anti-N IgG, triggered multifunctional Th1-biased T-cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals.
    Conclusion: These data suggest that VLPs expressing all four structural protein antigens of SARS-CoV-2 are immunogenic and can protect animals from developing COVID-19 infection following vaccination.
    MeSH term(s) Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; COVID-19 Vaccines ; HEK293 Cells ; Humans ; SARS-CoV-2 ; Vaccines, Virus-Like Particle
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Vaccines, Virus-Like Particle
    Language English
    Publishing date 2021-09-21
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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