Babel Lab: Viral Immunity und Immunomonitoring

Research profile/area

The main function of the immune system is to protect against infection by pathogens such as viruses, bacteria and fungi. Functional defects of the immune system can lead to an increased incidence of certain infections. For example, patients with immunodeficiency often suffer from chronic viral, bacterial or fungal infections. In contrast, defects in immune regulation often lead to autoimmune pathologies such as inflammatory bowel, skin or rheumatic diseases. In the case of common diseases such as osteoporosis or atherosclerosis, there is evidence that the immune system may play a decisive role in their pathogenesis.

Our research group employs a translational approach to investigate diseases in which the immune system plays a pathogenetic role. By this means we have generated knowledge and established model systems that are often applied directly in the diagnosis or treatment of immunological diseases. This combination of (viral) immunological expertise and our previous infrastructure is crucial for the quick and successful implementation of our knowledge in COVID-19 diagnostics and management.

In addition to establishing immunological tests for the assessment of specific anti-SARS-CoV-2 immunity, we have gained new insights into the immunopathogenic mechanisms of COVID-19. In addition, we have investigated extensively the effects of COVID-19 on the organism and the immunity of immunosuppressed and/or chronically ill patients. In this context, we identified a potential biomarker for the prediction of acute respiratory distress syndrome during COVID-19. In addition to their important diagnostic value, our research results have already been employed for the improvement of clinical treatment, especially of transplant patients.

The most important research areas of our group include:

  • Determination of the role of immune cells in the protection against infections (currently also COVID-19)
  • Study of the function of humoral and cellular immunity in the event of transplant rejection
  • Prediction of adverse immune reactions
  • Identification of prognostic markers for the disease course
  • Development of human in vitro model systems for therapy prediction and drug testing
  • Supervision of clinical studies to research immune-related pathologies – including common diseases such as osteoporosis and atherosclerosis

Publications

https://www.ncbi.nlm.nih.gov/pubmed/?term=nina+babel

  • Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients. Thieme CJ, et al. Cell Rep Med. 2020 Sep 22; 1(6): 100092. doi: 10.1016/j.xcrm.2020.100092 An analysis of the T cell immune response against three different SARS-CoV-2 antigens. We found no evidence of a positive effect of these immune responses on disease outcome.
  • Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans. Bacher P, et al. Cell. 2019 Mar 7;176(6):1340-1355.e15.  doi: 10.1016/j.cell.2019.01.041 Here we identify the immune response against the ubiquitous yeast Candida albicans as a mechanism for induction of Th17 cells and a risk factor for pulmonary inflammatory disease.
  • The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome. Thieme CJ, et al. Sci Rep. 2019 Dec 13;9(1):19037. doi: 10.1038/s41598-019-55442-x Here we describe an human model system for the prediction of rejection, employing urine samples taken before and after renal transplantation.
  • BK polyomavirus infection and nephropathy: the virus-immune system interplay. Babel N, Volk HD, Reinke P. Nat Rev Nephrol. 2011 May 24;7(7):399-406. doi: 10.1038/nrneph.2011.59 Comprehensive review about the challenges presented by BK virus infections after renal transplantation.
  • BKV, CMV, and EBV Interactions and their Effect on Graft Function One Year Post-Renal Transplantation: Results from a Large Multi-Centre Study. Blazquez-Navarro A, et al. EBioMedicine. 2018 Aug;34:113-121. doi: 10.1016/j.ebiom.2018.07.017 Results of a large, multi-centre study on the interactions between post-transplant viral infections and their influence on renal function.
  • The Role of Pre-existing Cross-Reactive Central Memory CD4 T-Cells in Vaccination With Previously Unseen Influenza Strains. Nienen M, et al. Front Immunol. 2019 Apr 4;10:593. doi: 10.3389/fimmu.2019.00593 Analysis of the cellular and humoral immune response after vaccination with a new Influenza strain. We identified the cross-reactivity with pre-existing T memory cells as a decisive factor for a positive vaccination outcome.
  • The Identity Card of T Cells-Clinical Utility of T-cell Receptor Repertoire Analysis in Transplantation. Babel N, Stervbo U, Reinke P, Volk HD. Transplantation. 2019 Aug;103(8):1544-1555. doi: 10.1097/TP.0000000000002776 A review on the potential applications of sequencing the T cell receptor repertoire for the monitoring of transplant recipients.

 

List of previously published work on COVID-19:

  • Stervbo U, Rahmann S, Roch T, Westhoff TH, Babel N. Epitope similarity cannot explain the pre-formed T cell immunity towards structural SARS-CoV-2 proteins. Science Rep 2020 Nov 4;10(1):18995; https://www.nature.com/articles/s41598-020-75
  • Anft M, Paniskaki K, Blazquez-Navarro A, Doevelaar AAN, Seibert FS et al. COVID-19-induced ARDS is associated with decreased frequency of activated memory/effector T cells expressing tissue migration molecule CD11a++. www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30535-9
  • Zgoura P, Seibert FS, Waldecker C, Doevelaar A, et al. Psychological Responses to the Coronavirus Disease 2019 Pandemic in Renal Transplant Recipients. Transplant Proc. 2020 Sep 3:S0041-1345(20)32710-X. doi: 10.1016/j.transproceed.2020.08.043. Online ahead of print.
  • Westmeier J, Paniskaki K, Karaköse Z, Werner T, et al. Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients.  mBio. 2020 Sep 18;11(5):e02243-20. doi: 10.1128/mBio.02243-20.
  • Thieme CJ, Anft M, Paniskaki K, Blazquez-Navarro A, et al. Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients.  Cell Rep Med. 2020 Sep 22;1(6):100092. doi: 10.1016/j.xcrm.2020.100092. Epub 2020 Aug 29.
  • Doevelaar AAN, Hölzer B, Seibert FS, Bauer F, et al. Lessons for the clinical nephrologist: recurrence of nephrotic syndrome induced by SARS-CoV-2.  J Nephrol. 2020 Sep 5:1-4. doi: 10.1007/s40620-020-00855-5. Online ahead of print.
  • Seidel M, Hölzer B, Appel H, Babel N, Westhoff TH; Impact of renal disease and comorbidities on mortality in hemodialysis patients with COVID-19: a multicenter experience from Germany.  COVID Dialysis Working Group. J Nephrol. 2020 Aug 17:1-4. doi: 10.1007/s40620-020-00828-8. Online ahead of print.
  • Babel N, Anft M, Blazquez-Navarro A, Doevelaar AAN, et al. Immune monitoring facilitates the clinical decision in multifocal COVID-19 of a pancreas-kidney transplant patient.  Am J Transplant. 2020 Aug 10:10.1111/ajt.16252. doi: 10.1111/ajt.16252. Online ahead of print.
  • Westhoff TH, Seibert FS, Bauer F, Stervbo U, Anft M, et al. Allograft infiltration and meningoencephalitis by SARS-CoV-2 in a pancreas-kidney transplant recipient. Am J Transplant. 2020 Jul 26. doi: 10.1111/ajt.16223. Online ahead of print.

 

Team

Prof. Dr. Nina Babel
Principal investigator
E-Mail: nina.babel@charite.de

Dr. rer. nat. Toralf Roch
Research assistant
E-Mail: toralf.roch@charite.de

Dr. rer. nat.  Arturo Blázquez Navarro
Research assistant
E-Mail: arturo.blazquez-navarro@charite.de

Dipl.-Biochem. Patrizia Wehler
Medical laboratory technician
E-Mail: patrizia.wehler@charite.de

Sviatlana Kaliszczyk
Medical laboratory technician
E-Mail: sviatlana.kaliszczyk@charite.de

Constantin Joachim Thieme
Research assistant
E-Mail: constantin.thieme@charite.de

Wera Pustlauk
Research assistant
E-Mail: wera.pustlauk@charite.de

Lema Safi
Medical doctoral candidate
E-Mail: lema.safi@charite.de

Larissa Anthofer
Master’s degree student
E-Mail: larissa.anthofer@charite.de

Kita Schmidt
Master’s degree student
E-Mail: kita.schmidt@charite.de

Ioanna Maria Dimitriou
Master’s degree student
E-Mail: ioanna-maria.dimitriou@charite.de

Isabel Neumann
Bachelor’s degree student
E-Mail: isabel.neumann@charite.de

 

Second research group in the Centre for Translational Medicine  in the Marien Hospital Herne of the Ruhr University Bochum:

Sandra Dunn
Secretary
E-Mail: sandra.dunn@elisabethgruppe.de

Dr. rer. nat. Ulrik Stervbo
Research assistant
E-Mail: ulrik.stervbo@elisabethgruppe.de

Dr. rer. nat.  Moritz Anft
Research assistant
E-Mail: moritz.anft@elisabethgruppe.de

Dr. med. Adrian Atilla Nicolas Doevelaar
Assistant physician
E-Mail: adrian-atila-nicolas.doevelaar@elisabethgruppe.de

Julia Kurek
Medical laboratory technician
E-Mail: julia.kurek@elisabethgruppe.de

Jan Zapka
Medical laboratory technician
E-Mail: jan.zapka@elisabethgruppe.de

Sarah Skrzypczyk
Medical laboratory technician
E-Mail: sarah.skrzypczyk@elisabethgruppe.de

Eva Kohut
Study Nurse
E-Mail: eva.kohut@elisabethgruppe.de

Melanie Streichhahn
Study Nurse
E-Mail: melanie.streichhahn@elisabethgruppe.de

Krystallenia Paniskaki
Assistant physician and doctoral candidate
E-Mail: krystallenia.paniskaki@uk-essen.de

Projects

e:Kid – Systems medicine approach for the personalization of immunosuppression after renal transplantation (Charité / Humboldt-Universität / Fraunhofer Institut / Epiontis GmbH / MicroDiscovery GmbH) (www.e-kidney.de)

OsteoSys – Investigation of osteoporosis in the context of cardiovascular complications and chronical inflammation. (Charité / Ruhr-Universität Bochum / Uniklinikum Essen / Fraunhofer Institut / Beckman Coulter Life)

NoChro – Early detection of pain chronification: An analytical application for the integration of sensory profiles and bio-markers (Charité / Ruhr-Universität Bochum / Medipan GmbH / MicroDiscovery GmbH / Fraunhofer Institut / Uniklinikum Schleswig-Holstein)

mTDM-immun – Mobile therapeutical monitoring of immunosuppression (Charité / Fraunhofer Institut / MicroDiscovery GmbH)

SepsisDataNet.NRW EU – Development of a sepsis bio-assay and of a decision support module for the personalization of sepsis treatment – tailored for their immunological state (Charité / Ruhr-Universität Bochum / Universität Witten / Uniklinikum Münster)

MicModeI2T – Modular image analysis platform for the integration of microscopic image-based data from biopsies into mathematical models of interactions between immune and target cells (Charité / Ruhr-Universität Bochum / MH Hannover / TU München / Helmholtz München / BIOMAX Informatics AG)

Development of peptide-based immunoassays for the prediction of complications in the post-transplant period (Charité / Humboldt-Universität / Fraunhofer Institut / Medipan GmbH / Biosynthan GmbH / PolyAnGmbH)

Investigation of the role of IL-17 on delayed graft function and alloimmunity in kidney transplant recipients (Charité)

Development of new diagnostic and monitoring tools for infections as well as new procedures for cost-effective diagnosis (Charité / Université Pierre et Marie Curie, Paris / Hadassah University Hospital, Israel / Epiontis GmbH)

Analysis of the interactions between viruses and the immune system (Charité / MPI / Humboldt-Universität)

Evaluation of the therapeutic potential of regulatory T cells in human and murine lupus (Charité / Uniklinikum Schleswig-Holstein)

Suppression of unwanted immune reactions (Charité / Uniklinikum Schleswig-Holstein)

Research into the immunomodulatory effects of erythropoietin (Charité)

Investigation of the effect of tacrolimus switch on cellular immunity (Charité / Ruhr-Universität Bochum)

Characterization of the Epstein-Barr virus-specific T cell immune response under different immunosuppressive conditions (Charité / Ruhr-Universität Bochum)

Determination of the effects of cytomegalovirus-specific antibodies on the cellular immune response against the cytomegalovirus and against the graft (Charité / Ruhr-Universität Bochum)

Characterization of HBV-specific cellular and humoral immunity in patients with chronic kidney failure (Charité / Ruhr-Universität Bochum)

Below we describe a selection of our research lines on the COVID-19 pandemic:

  • Identification of immunodominant epitopes of the SARS-CoV-2 virus
  • Sequencing of the lymphocyte receptor repertoire (TCR and BCR) to predict the antiviral protection of SARS-CoV-2 individuals, both exposed and unexposed
  • Quantification of SARS-CoV-2-specific cellular and humoral immunity and its functionality in transplant populations and other patients under immunosuppression
  • Identification of prognostic immunological biomarkers for the prediction of acute respiratory distress syndrome in COVID-19
  • Investigation of the mechanism of COVID-19-associated thrombotic microangiopathy
  • Detection of SARS-CoV-2-specific B memory cells to define long-term COVID-19 immunity
  • Characterization of the clinical outcome and immune system of COVID-19 patients with impaired renal function
  • Immune monitoring of COVID-19 patients treated with Remdesivir
  • Establishment and validation of tests for the routine diagnosis of SARS-CoV-2 reactive T-cell immunity in COVID-19
  • Establishment of an in vitro model system to investigate the immunogenicity of the SARS-CoV-2 proteins expressed in human cell lines
  • Establishment of an immune monitoring tool for nasopharyngeal swabs through epigenetic cell counting
  • Analysis of the effects of immunosuppressants on the SARS-CoV-2-lifecycle

Methods

  • Multiparameter flow cytometry analysis
  • T- and B-cell receptor NGS sequencing
  • Detection of virus-specific immune cells
  • Virus-specific qPCR from blood and serum to quantify viral load
  • mRNA transfection for mechanistic studies
  • Cultivation of primary immune cells, cells from urine and smooth muscle cells isolated from atherosclerotic tissue
  • Cytokine expression analysis by multiplex assay
  • Evaluation of large clinical studies
  • Application and translation of the research results into routine diagnostics and therapy

 

Training / Teaching

The training of physicians (including clinician scientists) and their integration into the scientific community is a main concern of our research group.

We are also very committed to training life scientists who want to work translationally for their bachelor’s, master’s and doctoral theses.

Funding / Cooperation

National partners

  • Medizinische  Klinik I - Allgemeine Innere, Nephrologie, Gastroenterologie, Pneumologie. Marien Hospital Herne - Universitätsklinikum der Ruhr-Universität Bochum. Prof. Dr. T. Westhoff, Dr. F. Bauer.
  • Rheumazentrum Ruhrgebiet. Prof. Dr. Braun, Dr. X. Baraliakos.
  • Knappschaftskrankenhaus Bochum. Ruhr-Universität Bochum. Prof. Dr. R. Viebahn.
  • Proteomcenter. Ruhr-Universität Bochum. Prof. Dr. K. Marcus, Dr. C. May.
  • Institut für Bioinformatik. Universitätsklinikum Essen. Prof. Dr. S. Rahmann.
  • Institut für Virologie. Ruhr-Universität Bochum. Prof. Dr. M. Tenbusch.
  • Fraunhofer Institut für Angewandte Informationstechnik FIT. Prof. Dr. H. Mathis, Dr. A. Linnemann.
  • Hämatologisch-Onkologisches Kompetenzzentrum DIAKO. Bremen. Prof. Dr. R. Trappe.
  • Klinik für Allgemein-, Viszeral-, und Transplantationschirurgie. Charité, Berlin. PD Dr. A. Pascher.
  • Institut für Medizinische Immunologie. Charité, Campus Virchow, Berlin. Prof. Dr. H.-D. Volk, Prof. Dr. B. Sawitzki.
  • Klinik für Nephrologie. Charité, Berlin. Prof. Dr. P. Reinke, Dr. L. Liefeldt.
  • Klinik für Gastroenterologie. Charité, Berlin. Prof. Dr. B. Siegmund, Prof. Dr. D. Baumgart.
  • Klinik für Rheumatologie. Charité, Campus Mitte. Dr. T. Alexander, Dr. J. Hummrich.
  • Klinik für Hämatologie. Charité, Campus Virchow. Prof. Dr. R. Arnold, PD Dr. I. Na.
  • Klinik für Transfusionsmedizin. Charité, Campus Virchow. Dr. C. Schönemann, Dr. N. Lachmann.
  • Klinik für Dermatologie. Charité, Campus Mitte. Dr. C. Ulrich, Dr. R. Sabat, Dr. K. Wolk.  
  • Berliner Center für Regenerative Therapien. Charité, Campus Virchow. Prof. Dr. A. Thiel, Prof. Dr. G. Duda.
  • Institut für Med. Genetik. Charité. Prof. Dr. S. Mundlos, Prof. Dr. N. Robinson. 
  • Institut für Theoretische Biologie. Humboldt-Universität zu Berlin. Dr. M. Or-Guil. 
  • Max-Planck Institut für Molekulare Genetik. Dr. B. Timmermann.
  • Deutsches Rheumaforschungzentrum. Dr. C. Romagnani, Prof. Dr. A. Scheffold.
  • Fraunhofer Institut für Zelltherapie. Dr. H. Seitz, Dr. C. Schröder, Dr. O. Gros. 
  • Epiontis GmbH. Dr. S. Olek, Dr. U. Baron. 
  • Generic Assays GmbH. Dr. D. Roggenbuck. 
  • Miltenyi GmbH. Dr. S. Wild.
  • Beckman Coulter GmbH. Dr. M. Kaymer, Dr. R. Gödde 

International partners

  • Experimental Hematology. Cleveland Clinic, Ohio, USA. Prof. J. Maciejewski.
  • Department of Immunology. Brighton and Sussex Medical School, GB. Prof. Dr. F. Kern.
  • Department of Pediatrics and Immunology. Baylor College of Medicine; TX, USA. Prof. Dr. C. Rooney.
  • Med. Clinic for Nephrology. Prague University. Prof. Dr. O. Viclicky. 
  • Department of Immunology. Université Pierre et Marie Curie, Paris. Prof. Dr. G. Gorochov. 
  • Department of Mathematics. Bar-Ilan University, Tel Aviv, Israel. Prof. Dr. Y Louzoun. 
  • Department of Bioinformatics. Centre National de la Recherche Scientifique. Prof. Dr. T. Morra. 
  • Institute and Clinic of Immunology; Academy of Science, Novosibirsk, Russland. Dr. E. Gavrilova, Prof. Dr. V. Kozlov
  • Department of Immunology. University Milano. Prof. Dr. J. Geginat.
  • Center for Genomic Regulation, Barcelona. Dr. J. Hecht  

Links to our websites