LABORATORY OF EXPERIMENTAL IMMUNOTHERAPY – The Stephan Angeloff Institute of Microbiology

The Laboratory of Experimental immunotherapy has a research program streamlined by the common goal of bringing novel immunological concepts to therapeutic approaches applicable in the clinic. The group of Prof. Dr. Tchavdar Vassilev is a leader in research on immunoregulatory properties of intravenous immunoglobulin preparations. The team is recognized for its competence and discoveries in the field of induced polyspecificity of antibodies, especially with the impressive results in the experimental treatment of sepsis using modified immunoglobulin preparations. Assoc. Prof. Anastas Pashov and his group studied the molecular mechanisms of immunogenicity of biologicals and the structural basis of antibody specificity and polyspecificity. Following the overall strategy of the laboratory to actively explore immunological approaches based on new systems biology paradigms, this team dedicated the last years to the development of a new direction in immunodiagnostics – the systematic analysis of antibody repertoires. This experimental program opens the way for a diversification of the OMICS technologies in immunology. Omics approaches in diagnostics and therapy are also the focus of the third line of investigations. The team of Assoc. Prof. Petya Dimitrova is dedicated to developing of a high-content Cellomics platform for drug screening and discovery. The efforts are directed to the development and implementation of precise multi-parametric analysis for studying the alterations in immune cellular functions after treatment with natural compounds, small molecule inhibitors of histone deacetylases and inhibitors of kinases associated with metabolic signaling pathways in autoimmune diseases and disorders, associated with chronic inflammation.

The Laboratory of Experimental immunotherapy regularly wins grants from the National Research Fund and International Funding sources, eg .: EU FP; NATO; Internal Funding of the Network of the Pasteur Institutes; Bilateral collaboration grants with France and Switzerland; Mechanism of the European Economic Area with Norway

PROJECTS:.

2020-2023: FNI, КP-06-Н37/24: Intelligent platform for management, analysis and integration of large arrays of biomedical data. CoPI: Assoc. Prof. Anastas Pashov, PI: Assoc. Prof. V Gancheva, Technical University -Sofia.

2020-2023: ACIP, m6A_RAIAV: The lung epitranscriptome and chromatin accessibility landscape in rheumatoid arthritis complicated by the flu. PI: Milena Leseva. CoPI: Dr. M. Hasan, Institute Pasteur-Paris, France, CoPI: S. Barbezange, Sciensano Belgium. Link: www.projectimmunolbg.com

2020-2021: FNI, КP-06-Н33/5: Comparative characteristics of exome spectra and antibody repertoire in Bulgarian patients with Alzheimer’s, fronto-temporal and unspecified dementia. CoPI: Assoc. Prof. Anastas Pashov, PI: dr. S. Kacharnak, Мedical University-Sofia.

2018-2021: FNI, КP-06–Н21/14: Antiphospholipid antibody reactivity profile in women with habitual abortion. CoPI: Assoc. Prof. Anastas Pashov, PI: dr. S. Pashova, IBIR-BAS.

2019-2021: КP-06-Russia-5. Polyspecificity of immunoglobulin A and G. PI: Assoc. Prof. Petya Dimitrova in collaboration with dr. Еkaterina Gorshkova, Lobachevski State University of Nizhni Novgorod, Russia. Link: www.projectimmunolbg.com

2017-2021: DN 11/5_2017. Sirtuins (SIRTs)- new target for fine-tuning of epigenetic regulation of the joint inflammation during flu infections. PI: Assoc. prof. Petya Dimitrova in collaboration with dr. Lora Simeonova, Department of Virology, The Stephan Angeloff Institute of Microbiology, BAS. Link: www.projectimmunolbg.com

2016-2021: NSF DN01-64. Proteomic analysis of the repertoire of IgM antibodies in patients with brain tumors. PI: Assoc. Prof. Anastas Pashov, in collaboration with Dr. Dilyan Ferdinandov from the Sofia Medical University.

2015-2017: NSF B02/275. Physiological role and therapeutic potential of antibodies with induced polyspecificity. PI: Prof. Tchavdar Vassilev.

2015-2017: EEA Grants, Program BG09, D03-103. Rational design of antibody repertoire probes using peptide arrays. PI: Assoc. Prof. Anastas Pashov, in collaboration with Prof. Eivind Hovig from the Tumor Immunology Department of the Oslo University Hospital, Norway.

2012-2015: SNSF IZEBZO_142967: Design of modified immunoglobulin preparations with induced polyspecificity for passive immunotherapy of sepsis. PI: Prof. Tchavdar Vassilev.

2012-2017: Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk (ABIRISK). Consortium in the framework of IMI. Prof. Anastas Pashov participated as a collaborator to INSERM U872, Paris in WP3.

2012-2014: ACIP A07-2012. Therapeutic potential of modified pooled IgM and IgG preparations in experimental severe inflammatory response syndrome (SIRS) and sepsis. PI: Prof. Tchavdar Vassilev.

2010-2013: FP7-PEOPLE-2009-RG 248289, Marie Curie International Re-integration Grants (IRG). Translational study on the antigen presenting properties of human vs mouse B cell subpopulations. PI: Assoc. Prof. Anastas Pashov

2011-2013: ACIP/A05_11. The role of neutrophils and NK cells in the development of collagenase-induced osteoarthritis. PI: Assoc. Prof. Petya Dimitrova, Institute of Microbiology-Sofia, in collaboration with Prof. Angela Santoni, University La Sapienza-Rome and Dr. Crina Stavaru, Cantacuzino Institute-Bucharest

SELECTED PUBLICATIONS:

• Shivarov, V, Petrov, P, Pashov, A.D. Potential SARS-CoV-2 Preimmune IgM Epitopes. Frontiers in Immunology, 11, 932, 2020, ISSN:1664-3224, DOI:10.3389/fimmu.2020.00932, 1-5. SJR (Scopus):2.112, JCR-IF (Web of Science):5.085, Q1 (Scopus), .
• Planchais, C, Rayes, J, Pashova, S, Varthaman, A, Pashov, A, Bayry, J, Kaveri, S, Dimitrov, J. D, Lacroix-Desmazes, S. Stimulation with FITC-labeled antigens confers B cells with regulatory properties. Cellular Immunology, 355, 104151, 2020, ISSN:1090-2163, DOI:10.1016/j.cellimm.2020.104151, 1-8. JCR-IF (Web of Science):3.1 Q2 (Scopus)
• Dimitrova, PA, Alipieva, K, Grozdanova, T, Leseva, M, Gerginova, D, Simova, S, Marchev, AS, Bankova, V, Georgiev, MI, Popova, MP. Veronica austriaca L. Extract and Arbutin Expand Mature Double TNF-/IFN- Neutrophils in Murine Bone Marrow Pool. Molecules, 25, 15, MDPI, 2020, ISSN:1420-3049, DOI:doi:10.3390/molecules25153410, 3410. SJR (Scopus):0.698, JCR-IF (Web of Science):3.267 Q1 (Web of Science)
• Leseva, M, Binder, AM, Ponsonby, AL, Vuillermin, P, Saffery, R, Michels, KB, BIS Investigator Group. Differential gene expression and limited epigenetic dysregulation at the materno-fetal interface in preeclampsia. Human Molecular Genetics, Oxford University Press, 2019, ISSN:0964-6906, DOI:doi: 10.1093/hmg/ddz287, SJR (Scopus):2.89, JCR-IF (Web of Science):4.544 Q1 (Web of Science)
• Kohler, H, Pashov, A, Kieber-Emmons, T. The Promise of Anti-idiotype Revisited. Frontiers in Immunology, 10, 808, 2019, ISSN:1664-3224, DOI:10.3389/fimmu.2019.00808, SJR (Scopus):2.116, JCR-IF (Web of Science):5.085 Q1 (Scopus)
• Kohler, H, Pashov, A, Kieber-Emmons, T. Commentary: Immunology’s Coming of Age. Frontiers in Immunology, 10, 2175, 2019, ISSN:1664-3224, DOI:10.3389/fimmu.2019.02175, SJR (Scopus):2.116, JCR-IF (Web of Science):5.03 Q1 (Scopus)
• Pashov, A, Shivarov, V, Hadzhieva, M, Kostov, V, Ferdnandov, D, Heintz, K.-M, Pashova, S, Todorova, M, Vassilev, T, Kieber-Emmons, T, Meza-Zepeda, L.A, Hovig, E. Diagnostic Profiling of the Human Public IgM Repertoire With Scalable Mimotope Libraries. Frontiers in Immunology, 10, 2796, 2019, ISSN:1664-3224, DOI:10.3389/fimmu.2019.02796, SJR (Scopus):2.116, JCR-IF (Web of Science):5.085 Q1 (Scopus)
• Pashov, A, Kieber-Emmons, T. Mimetic Vaccines in Immuno-Oncology. Cancer Immunotherapy and Biological Cancer Treatments, IntechOpen, 2019, DOI:10.5772/intechopen.85593
• Amirova, K, Dimitrova, P, Marchev, A, Aneva, Y, Georgiev, M. Clinopodium vulgare L. (wild basil) extract and its active constituents modulate cyclooxygenase-2 expression in neutrophils. Food and Chemical Toxicology, 124, Elsevier, 2019, ISSN:0278-6915, DOI:10.1016/j.fct.2018.11.054, 1-9. JCR-IF (Web of Science):4.679 Q1 (Scopus)
• Dimitrova, P, Alipieva, K, Stojanov, K, Milanova, V, Georgiev, MI. Plant-derived verbascoside and isoverbascoside regulate Toll-like receptor 2 and 4-driven neutrophils priming and activation. Phytomedicine, 55, 1, Elsevier, 2019, ISSN:0944-7113, DOI:10.1016/j.phymed.2018.07.013, 105-118. JCR-IF (Web of Science):4.268 Q1 (Scopus)
• Vassilev, T.L., Kostov, V, von Gunten, V., Pashov, A.D.. Basics of Immunoglobulins as Effector Molecules and Drugs. Antibody Therapy Substitution – Immunomodulation – Monoclonal Immunotherapy, Springer Nature Switzerland AG, 2018, ISBN:978-3-319-68038-5, DOI:10.1007/978-3-319-68038-5_11, 13, 133-150
• Pashov, A, Shivarov, V, Hadzhieva, M, Kostov, V, Ferdinandov, D, Heinz, K.-M, Pashova, S, Todorova, M, Vassilev, T.L, Kieber-Emmons, T, Meza-Zepeda, L. A, Hovig, E. A rationally designed mimotope library for profiling of the human IgM repertoire. bioRxiv.org, 2018, DOI:doi.org/10.1101/308973
• Pashov, A, Hernandez-Puente, C.V., Ibrahim, S.M., Monzavi-Karbassi, B., Makhoul, I, Kieber-Emmons, T. Thinking Cancer. Monoclon Antib Immunodiagn Immunother, 37, 3, Mary Ann Liebert, 2018, ISSN:2167-9436, DOI:10.1089/mab.2018.0014, 117-125. SJR (Scopus):0.583, JCR-IF (Web of Science):3.1 Q3 (Scopus)
• Leseva, M, Grand, R, Klett, H, Boerries, M, Busch, H, Binder, A, Michels, K. Differences in DNA Methylation and Functional Expression in Lactase Persistent and Non-persistent Individuals. Scientific Reports, 8, 1, Nature Publishing Group, 2018, ISSN:2045-2322, DOI:doi: 10.1038/s41598-018-23957-4, SJR (Scopus):1.414, JCR-IF (Web of Science):4.011 Q1 (Web of Science)
• Dimitrova, P, Alipieva, K, Grozdanova, T, Simova, S, Bankova, V, Georgiev, MI, Popova, MP. New iridoids from Verbascum nobile and their effect on lectin-induced T cell activation and proliferation. Food and Chemical Toxicology, 111, January, Elsevier, 2018, ISSN:0278-6915, DOI:10.1016/j.fct.2017.11.060, 605-615. SJR (Scopus):1.024, JCR-IF (Web of Science):3.775 Q1 (Scopus)
• Schneider, C, Wicki, S, Graeter, S, Timcheva, TM, Keller, CW, Quast, I, Leontyev, D, Djoumerska-Alexieva, IK, Käsermann, F, Jakob, SM, Dimitrova, PA, Branch, DR, Cummings, RD, Lünemann, JD, Kaufmann, T, Simon, H-U, von Gunten, S. IVIG regulates the survival of human but not mouse neutrophils. Scientific Reports, May, 7, Nature Publishing, 2017, ISSN:2045-2322, DOI:10.1038/s41598-017-01404-0, 1296. SJR (Scopus):1.625, JCR-IF (Web of Science):4.847 Q1 (Web of Science)
• Pashova, S, Schneider, Chr, von Gunten, S, Pashov, S. Antibody Repertoire Profiling with Mimotope Arrays. Human Vaccines and Immunotherapy, Taylor&Francis, 2017, DOI:10.1080/21645515.2017.1264786, SJR (Scopus):0.984, JCR-IF (Web of Science):2.146 Q2 (Web of Science)
• Murali, R, Saha, S, Pashov, A, Kieber-Emmons, T. Summarizing Solvation Effects on Antibody Structure and Function.. Journal of Nature and Science, 3, 7, 2017, ISSN:2377-2700, e402
• Hutchins, LF, Makhoul, I, Emanuel, P, Pennisi, A, Siegel, E, Jousheghany, F, Guo, X, Pashov, A, Monzavi-Karbassi, B, Kieber-Emmons, T. Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects. Oncotarget, 8, 58, 2017, ISSN:1949-2553, DOI:10.18632/oncotarget.21959, 99161-99178. SJR (Scopus):1.942, JCR-IF (Web of Science):5.17 Q1 (Scopus)
• Gilardin, L, Delignat, S, Peyron , I, Ing, M, Lone, Y-Ch, Gangadharan, B, Michard, B, Kherabi, Y, Sharma, M, Pashov, A, Latuche, J-B, Hamieh, M, Toutirais, O, Loiseau, P, Galicier, L, Veyradier, A, Kaveri, S, Maillere, B, Coppo, P, Lacroix-Desmazes, S. The ADAMTS131239-1253 peptide is a dominant HLA-DR1-restricted CD4+ T-cell epitope. Haematologica, 102, 11, 2017, ISSN:1592-8721, DOI:10.3324/haematol.2015.136671, 1833-1841. JCR-IF (Web of Science):7.7 Q4 (Scopus)
• Benigni, G, Dimitrova, P, Antonangeli, F, Sanseviero, E, Milanova, V, Blom, A, van Lent, P, Morrone, S, Santoni, A, Bernardini, G. CXCR3/CXCL10 Axis Regulates Neutrophil–NK Cell Cross-Talk Determining the Severity of Experimental Osteoarthritis. Journal of Immunology, March, 198, American Association of Immunologists, 2017, ISSN:0022-1767, DOI:https://doi.org/10.4049/jimmunol.1601359, 2115-2124. SJR (Scopus):3.368, JCR-IF (Web of Science):4.539 Q1 (Scopus)
• Marchev, A, Dimitrova, P, Burns, A, Kostov, R, Dinkova-Kostova, A, Georgiev, M. Oxidative stress and chronic inflammation in osteoarthritis: can Nrf2 counteract these partners in crime?. Annals of the New York Academy of Sciences, 1, 1401, Wiley Online Library, 2017, DOI:10.1111/nyas.13407, 114-135. SJR (Scopus):2.11, JCR-IF (Web of Science):4.277 Q1 (Scopus)
• Marchev, A, Dimitrova, P, Koycheva, I, Georgiev, M. Altered expression of TRAIL on mouse T cells via ERK phosphorylation by Rhodiola rosea L. and its marker compounds. Food and Chemical Toxicology, Part 2, 108, Elsevier, 2017, DOI:10.1016/j.fct.2017.02.009, 419-428. SJR:1.14, ISI IF:3.977 Q1,(Scopus)
• Hadzhieva, M, Pashov, A, Kaveri, S, Lacroix- Desmazes, S, Mouquet, H, Dimitrov, J. Impact of Antigen Density on the Binding Mechanism of IgG Antibodies. Scientific Reports, 7, Springer Nature, 2017, ISSN:2045-2322, DOI:10.1038/s41598-017-03942-z, 3767. SJR (Scopus):1.533, JCR-IF (Web of Science):4.26 Q1, не оглавява ранглистата (Web of Science)
• Djoumerska-Alexieva, I, Stefanova, T, Vassilev, T, Roumenina, L.T, Dimitrov, J.D. Heme-Exposed Pooled Therapeutic IgG Improves Endotoxemia Survival.. Inflammation, 40, 19, 2017, ISSN:0360-3997, 117-122. SJR (Scopus):0.942, JCR-IF (Web of Science):2.618 Q2 (Scopus)
• Djoumerska-Alexieva, I, Roumenina, L, Pashov, A, Dimitrov , J, Hadzhieva, M, Lindig, S, Voynova, E, Dimitrova, P, Ivanovska, N, Bockmeyer, C, Stefanova, Z, Fitting, C, Bläss, M, Ralf, S, von Guten, S, Kaveri, S, Cavillon, J-M, Bauer, M, Vassilev, T. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes. Molecular Medicine, 21, 1, North Shore – Long Jewish Research Institute, 2016, ISSN:1528-3658, DOI:10.2119/molmed.2014.00224, 1002-1010. SJR:1.449, ISI IF:4.508 Q2 (Scopus)
• Schneider, C, Smith, D.F, Cummings, R.D, Boligan, K.F, Hamilton, R.G, Bochner, B.S, Miescher, S, Simon, H.-U, Pashov, A, Vassilev, T, von Gunten, S. The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites.. Science Translational Medicine, 7, 269, 2015, 269ra1. SJR (Scopus):9.859, JCR-IF (Web of Science):16 Q1 (Scopus)

PATENTS:.

WO2014US49309 20140731/US 61860827: KIEBER-EMMONS THOMAS [US]; PASHOV ANASTAS [US]; KARBASSI BEHJATOLAH [US] . COMPOSITIONS FOR AND METHODS OF TREATING AND PREVENTING CANCER TARGETING TUMOR ASSOCIATED CARBOHYDRATE ANTIGENS.
EP 1 838 731 B1. T.L. VASSILEV, J.D. DIMITROV. USE OF FERROUS IONS FOR INCREASING THE IMMUNOREACTIVITY OF IMMUNOGLOBULIN PREPARATIONS.
65787 B1. (54) Ч.Л. ВАСИЛЕВ, Й. Д. ДИМИТРОВ. СРЕДСТВО ЗА ПОВИШАВАНЕ НА АНТИГЕН-СВЪРЗВАЩАТА АКТИВНОСТ НА ИМУНО-ГЛОБУЛИНОВИ ПРЕПАРАТИ.