Araştırma Çıktıları
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Item Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice(NATURE PORTFOLIO, 2021-01-01) Turan, Raife Dilek; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Karakus, Gozde Sir; Ozer, Samed; Abanuz, Selen; Cakirsoy, Didem; Tumentemur, Gamze; Demir, Sevda; Seyis, Utku; Kuzay, Recai; Elek, Muhammer; Kocaoglu, Miyase Ezgi; Ertop, Gurcan; Arbak, Serap; Elmas, Merve Acikel; Hemsinlioglu, Cansu; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Kayhan, Cavit Kerem; Tokat, Fatma; Akpinar, Gurler; Kasap, Murat; Kocagoz, Ayse Sesin; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ince, Umit; Ovali, ErcumentThe SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10(13) or 10(14) viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.Item Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates(NATURE RESEARCH, 2021-01-01) Karakus, Gozde Sir; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Tumentemur, Gamze; Demir, Sevda; Turan, Raife Dilek; Abanuz, Selen; Cakirsoy, Didem; Seyis, Utku; Ozer, Samed; Elibol, Omer; Elek, Muhammer; Ertop, Gurcan; Arbale, Serap; Elmas, Merve Acikel; Hermsinlioglu, Canso; Kocagoz, Ayse Sesin; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ovali, ErcumentCOVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1(V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2+ mice.Item Investigation of ceftazidime-avibactam susceptibility in clinical isolates of gram-negative bacteria(Scientific and Technological Research Council Turkey, 2022-01-01) Dumlu, Ridvan; Uyar, Neval Yurttutan; Ayas, Meltem; Aksoy, Nilay; Ozturk, Nur; Kocagoz, Ayse SesinBackground/aim: Our study investigated the susceptibility rate of ceftazidime-avibactam and the risk factors associated with its resistance by analyzing gram-negative bacteria isolated from various patient samples. Materials and methods: Between March and November 2020, 1119 gram-negative bacteria strains were isolated from patient samples in Acibadem Healthcare Group hospitalsItem Evaluation of patients who were followed with bacteremia in intensive care unit(CUKUROVA UNIV, FAC MEDICINE, 2019-01-01) Akyildiz, Ozay; Besli, Yesim; Kocagoz, Ayse SesinPurpose: In this study, the microorganisms isolated from the blood cultures of the patients who are hospitalized in the general intensive care unit (ICU) of our hospital were evaluated retrospectively and it was aimed to obtain the guiding data for the appropriate empirical treatment selection. Materials and Methods: Species distribution and antimicrobial susceptibility of 163 microorganisms, isolated from blood cultures of 152 inpatients aged 18 years and older were evaluated retrospectively. Blood cultures were taken during the febrile period of inpatients who stayed in clinic were incubated in blood culture media in BACTEC automated blood culture system. Results: Of these microorganisms found, 68\% (n=111) were Gram positive bacteria, 25\% (n=40) were Gram negative bacteria, and 7\% (n=12) were fungi. The most common microorganisms were coagulase negative staphylococcus (CoNS), Escherichia coli and Candida spp. Of the Gram negative agents isolated from blood cultures, 7\% (n=12) were Escherichia coli, 6\% (n=9) were Klebsiella spp., 5\% (n=8) were Pseudomonas spp., 4\% (n=6) were Acinetobacter spp. Extended Spectrum Beta Lactamase (ESBL) was detected 75\% (n=9) of E.coli, and 78\% (n=6) of Klebsiella spp. isolate. Conclusion: Epidemiological information about species distribution and antibiotic resistance of the isolated infectious agents and will contribute to the determination of their antibiotic usage and to decrease the morbidity and mortality rates.Item Mutational landscape of SARS-CoV-2 genome in Turkey and impact of mutations on spike protein structure(PUBLIC LIBRARY SCIENCE, 2021-01-01) Hatirnaz Ng, Ozden; Akyoney, Sezer; Sahin, Ilayda; Soykam, Huseyin Okan; Bayram Akcapinar, Gunseli; Ozdemir, Ozkan; Kancagi, Derya Dilek; Sir Karakus, Gozde; Yurtsever, Bulut; Kocagoz, Ayse Sesin; Ovali, Ercument; Ozbek, UgurThe Coronavirus Disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). As of May 25th, 2021 there were 2.059.941 SARS-COV2 genome sequences that have been submitted to the GISAID database, with numerous variations. Here, we aim to analyze the SARS-CoV-2 genome data submitted to the GISAID database from Turkey and to determine the variant and clade distributions by the end of May 2021, in accordance with their appearance timeline. We compared these findings to USA, Europe, and Asia data as well. We have also evaluated the effects of spike protein variations, detected in a group of genome sequences of 13 patients who applied to our clinic, by using 3D modeling algorithms. For this purpose, we analyzed 4607 SARS-CoV-2 genome sequences submitted by different lab centers from Turkey to the GISAID database between March 2020 and May 2021. Described mutations were also introduced in silico to the spike protein structure to analyze their isolated impacts on the protein structure. The most abundant clade was GR followed by G, GH, and GRY and we did not detect any V clade. The most common variant was B.1, followed by B.1.1, and the UK variant, B.1.1.7. Our results clearly show a concordance between the variant distributions, the number of cases, and the timelines of different variant accumulations in Turkey. The 3D simulations indicate an increase in the surface hydrophilicity of the reference spike protein and the detected mutations. There was less surface hydrophilicity increase in the Asp614Gly mutation, which exhibits a more compact conformation around the ACE-2 receptor binding domain region, rendering the structure in a ``down{''} conformation. Our genomic findings can help to model vaccination programs and protein modeling may lead to different approaches for COVID-19 treatment strategies.