Publications by authors named "Simon Fink"

5 Publications

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Multiplexed Serum Antibody Screening Platform Using Virus Extracts from Endemic and SARS-CoV-2.

ACS Infect Dis 2021 Mar 16. Epub 2021 Mar 16.

NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany.

The presence of antibodies against endemic coronaviruses has been linked to disease severity after SARS-CoV-2 infection. Assays capable of concomitantly detecting antibodies against endemic coronaviridae such as OC43, 229E, NL63, and SARS-CoV-2 may help to elucidate this question. We developed a serum screening platform using a bead-based Western blot system called DigiWest, capable of running hundreds of assays using microgram amounts of protein prepared directly from different viruses. Characterization of the immunoassay for detection of SARS-CoV-2 specific antibodies revealed a sensitivity of 90.3% and a diagnostic specificity of 98.1%. Concordance analysis with the SARS-CoV-2 immunoassays available by Roche, Siemens, and Euroimmun indicates comparable assay performances (Cohen's κ ranging from 0.8874 to 0.9508). Analogous assays for OC43, 229E, and NL63 were established and combined into one multiplex with the SARS-CoV-2 assay. Seroreactivity for different coronaviruses was detected with high incidence, and the multiplex assay was adapted for serum screening.
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http://dx.doi.org/10.1021/acsinfecdis.0c00725DOI Listing
March 2021

Nidogen-1 Mitigates Ischemia and Promotes Tissue Survival and Regeneration.

Adv Sci (Weinh) 2021 Feb 21;8(4):2002500. Epub 2020 Dec 21.

Department of Bioengineering Eberhard Karls University Tübingen Tübingen 72076 Germany.

Ischemia impacts multiple organ systems and is the major cause of morbidity and mortality in the developed world. Ischemia disrupts tissue homeostasis, driving cell death, and damages tissue structure integrity. Strategies to heal organs, like the infarcted heart, or to replace cells, as done in pancreatic islet -cell transplantations, are often hindered by ischemic conditions. Here, it is discovered that the basement membrane glycoprotein nidogen-1 attenuates the apoptotic effect of hypoxia in cardiomyocytes and pancreatic -cells via the v3 integrin and beneficially modulates immune responses in vitro. It is shown that nidogen-1 significantly increases heart function and angiogenesis, while reducing fibrosis, in a mouse postmyocardial infarction model. These results demonstrate the protective and regenerative potential of nidogen-1 in ischemic conditions.
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http://dx.doi.org/10.1002/advs.202002500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887579PMC
February 2021

Antibody Response against SARS-CoV-2 and Seasonal Coronaviruses in Nonhospitalized COVID-19 Patients.

mSphere 2021 02 24;6(1). Epub 2021 Feb 24.

Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany

The majority of infections with SARS-CoV-2 are asymptomatic or mild without the necessity of hospitalization. It is of importance to reveal if these patients develop an antibody response against SARS-CoV-2 and to define which antibodies confer virus neutralization. We conducted a comprehensive serological survey of 49 patients with a mild course of disease and quantified neutralizing antibody responses against a clinical SARS-CoV-2 isolate employing human cells as targets. Four patients (8%), even though symptomatic, did not develop antibodies against SARS-CoV-2, and two other patients (4%) were positive in only one of the six serological assays employed. For the remaining 88%, antibody response against the S protein correlated with serum neutralization whereas antibodies against the nucleocapsid were poor predictors of virus neutralization. None of the sera enhanced infection of human cells with SARS-CoV-2 at any dilution, arguing against antibody-dependent enhancement of infection in our system. Regarding neutralization, only six patients (12%) could be classified as high neutralizers. Furthermore, sera from several individuals with fairly high antibody levels had only poor neutralizing activity. In addition, employing a novel serological Western blot system to characterize antibody responses against seasonal coronaviruses, we found that antibodies against the seasonal coronavirus 229E might contribute to SARS-CoV-2 neutralization. Altogether, we show that there is a wide breadth of antibody responses against SARS-CoV-2 in patients that differentially correlate with virus neutralization. This highlights the difficulty to define reliable surrogate markers for immunity against SARS-CoV-2. There is strong interest in the nature of the neutralizing antibody response against SARS-CoV-2 in infected individuals. For vaccine development, it is especially important which antibodies confer protection against SARS-CoV-2, if there is a phenomenon called antibody-dependent enhancement (ADE) of infection, and if there is cross-protection by antibodies directed against seasonal coronaviruses. We addressed these questions and found in accordance with other studies that neutralization is mediated mainly by antibodies directed against the spike protein of SARS-CoV-2 in general and the receptor binding site in particular. In our test system, utilizing human cells for infection experiments, we did not detect ADE. However, using a novel diagnostic test we found that antibodies against the coronavirus 229E might be involved in cross-protection to SARS-CoV-2.
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http://dx.doi.org/10.1128/mSphere.01145-20DOI Listing
February 2021

Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity.

Nat Commun 2021 02 19;12(1):1152. Epub 2021 Feb 19.

NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.

The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses. Compared to three broadly used commercial in vitro diagnostic tests, our MultiCoV-Ab achieves a higher sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. We find a high response against endemic coronaviruses in our sample set, but no consistent cross-reactive IgG response patterns against SARS-CoV-2. Here we show a robust, high-content-enabled, antigen-saving multiplex assay suited to both monitoring vaccination studies and facilitating epidemiologic screenings for humoral immunity towards pandemic and endemic coronaviruses.
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http://dx.doi.org/10.1038/s41467-021-20973-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896075PMC
February 2021

Excellent Long-term Breast Preservation Rate After Accelerated Partial Breast Irradiation Using a Balloon Device.

Clin Breast Cancer 2016 06 11;16(3):217-22. Epub 2016 Feb 11.

Department of Radiation Oncology, New York-Presbyterian Hospital/Queens, Weill Cornell Medical College, New York, NY.

Background: Accelerated partial breast irradiation (APBI) using a balloon device has been well tolerated. A recent retrospective population-based study showed an increase in the rate of subsequent mastectomy for patients who undergo APBI compared with whole breast radiation therapy. Our aim was to analyze the long-term results of patients treated with APBI at our institution to determine the salvage mastectomy and locoregional recurrence rates and cosmesis outcomes.

Materials And Methods: After institutional review board approval, we conducted a retrospective review of 111 patients treated from June 2003 to October 2014 at our institution for early-stage breast cancer using a balloon device. After lumpectomy and nodal staging, the patients underwent APBI with high-dose rate iridium-192 brachytherapy. A computed tomography-based 3-dimensional plan was created, and a dose of 34 Gy in 10 fractions was given twice daily, 6 hours apart, over 5 days. Follow-up examinations were performed 2 to 3 times annually by either a surgeon and/or a radiation oncologist. Annual mammograms were obtained. The patients included postmenopausal women with node-negative early-stage invasive ductal carcinoma with a tumor size < 3 cm (n = 93) or ductal carcinoma in situ (n = 18). Cosmesis was evaluated using the Harvard criteria, as excellent, good, fair, or poor.

Results: At a median follow-up period of 66 months (range, 1-139 months) after completing treatment, with a minimum of 5 years of follow-up data for 62 patients (55.9%), the incidence of ipsilateral breast tumor recurrence (IBTR) was 2.7% (n = 3) and the incidence of ipsilateral axilla nodal recurrence was 1.8% (n = 2). The ipsilateral breast preservation rate was 97.3%. The salvage mastectomy rate was 2.7% (n = 3), and the 5-year salvage mastectomy-free rate was 98.7% (95% confidence interval, 91.0%-99.8%). No distant failure developed, and no breast cancer-related deaths occurred. The 5-year overall survival rate was 91.7% (95% confidence interval, 83.2%-96.0%), and the 10-year breast cancer-specific survival rate was 100%. Of the 3 cases of IBTR, 2 were estrogen receptor negative (P = .076). The mean interval to IBTR was 78.7 ± 27.5 months from treatment completion. A significant association was noted between African-American ethnicity and IBTR (P = .0398). Excellent to good cosmesis was observed in 98.1% of the patients. The maximum skin dose (mean value) for patients with excellent, good, and fair cosmesis was 302.2 Gy, 315.4 Gy, and 372.5 Gy (88.9%, 92.7%, and 109.5% of the prescription dose), respectively. The maximum skin dose was < 340 Gy (100% of the prescribed dose) in 69.9% of patients with excellent to good cosmesis.

Conclusion: The long-term follow-up data of patients receiving APBI with a balloon device showed a low salvage mastectomy rate with durable long-term breast preservation. Excellent local control with good cosmesis was noted in these postmenopausal patients treated with APBI.
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http://dx.doi.org/10.1016/j.clbc.2016.02.010DOI Listing
June 2016