LABORATORY OF EXPERIMENTAL IMMUNOTHERAPY

This project demonstrated the feasibility of representing large igomic arrays of mimotopes (n×106) with smaller, representative libraries (n×103). These libraries effectively address the highly degenerate IgM repertoire (with broad polyreactivity) and provide sufficient diversity to extract a vast number of different biomarkers for various conditions, such as different brain tumors. Each biomarker consists of a set of peptide mimotopes (n<102), whose reactivities form a specific profile with diagnostic value. Machine learning is employed, involving multi-stage feature selection and the creation of in silico models based on support vector machines (SVM). Searching for homologous sequences in the human proteome revealed that the most characteristic aspect of diagnostic peptides is that they are mimotopes of the CDR3 region (J-region) of other human antibodies. Thus, unexpectedly, an advanced technology for studying the antibody repertoire brought us back to a forgotten theory – the idiotype network.

Grant # DN 01-11. Proteomic Analysis of the IgM Antibody Repertoire in Patients with Brain Tumors. FNI. 2017-2021, Principal Investigator – Assoc. Prof. Anastas Pashov.

In the study of serum IgM reactivities from patients with brain tumors to 4500 peptides from known human tumor antigens, undirected graph of cross-reactivities was used as a new way to present the results of high-throughput antibody binding assays. The significant polyreactivity of IgM antibodies justifies this approach. It was found that a major factor determining the topology of the IgM reactivity graph is the reactivity to blood group antigens. As before, we managed to show the possibility of extracting profiles of peptide reactivities from these data, which classify different brain tumors (validated with the “leave one out” algorithm).

Grant # KP-06-N1/14. Profile of Antiphospholipid Antibody Reactivity in Women with Habitual Abortions. FNI, 2019-, Principal Investigator – Senior Assistant Shina Pashova, IBIR, BAS.

This project demonstrated that the igome can reveal intimate mechanisms of autoimmune diseases. In antiphospholipid syndrome, where the pathology-associated autoantibodies are of the IgG class, the IgM repertoire (likely natural) shows signs of restriction, or simply put, has "gaps" compared to that in healthy individuals. In this project, we introduced the bioinformatic representation of the igome as a graph of mimotope sequences connected when they share a common subsequence of 5/7 amino acid residues. This condition was determined by comparing isospecific pairs of mimotopes (derived using the same monoclonal template) with pairs of randomly selected peptides. The use of graphs unlocks a rich set of mathematical tools from graph theory, and prospectively, from topological data analysis (TDA).

Grant # KP-06-N33/5. Comparative Characterization of Exomic Spectra and Antibody Repertoire in Bulgarian Patients with Alzheimer's, Frontotemporal, and Unspecified Dementia. FNI, 2020-2024, Principal Investigator – Prof. Draga Toncheva (Assoc. Prof. Sena Karachanak-Yankova), MU Sofia.

The initial results of this project show that the IgM igome distinguishes types of dementia better than the IgG. Here, the optimized library of IgM mimotopes from our first project was used. For the first time, spectral embedding (or the eigenvectors of the graph Laplacian) in combination with the UMAP algorithm, which actually uses TDA, was employed for visualizing the reactivity graph (reagraph).

Grant # KP-06-DK1/5 SARSIMM. Searching for Ligands that Unblock the Innate Immune Response in SARS-Cov-2 Infected Cells. FNI, 2022-2024, Principal Investigator – Prof. Leander Litov, SU, Sofia.

Grant # KP-06-H37/24. Innovative Integrated Platform for Intelligent Management and Analysis of Large Data Streams for Biomedical Scientific Research. FNI, 2020-2024, Principal Investigator – Assoc. Prof. Veska Gancheva, TU, Sofia.

COST Action, EUTOPIA - European Topology Interdisciplinary Action, Prof. Nevena Ilieva-Litova, IICT, BAS.

Grant # KP-06-China-10/2020. New Method for In Silico Design of Peptide Biotherapeutics Based on Cyclotides. FNI, 2020-2023, Principal Investigator – Prof. Nevena Ilieva-Litova, IICT, BAS.

Publications related with TOPIC 1

1. Pashova-Dimova, S., P. Petrov, S. Karachanak-Yankova, A. Pashov.
 Neurodegenerative diseases associated antibody repertoire signatures in mimotope arrays based on cyclic versus linear peptides. Pharmacia 70 (2023) (4),1439-1447.
2. Ferdinandov, D., V. Kostov, M. Hadzhieva, V. Shivarov, P. Petrov, A. Bussarsky, A. D. Pashov. 
Reactivity Graph Yields Interpretable IgM Repertoire Signatures as Potential Tumor Bi-omarkers. International Journal of Molecular Sciences 24 (2023) (3),2597.
3. Pashova, S., L. Balabanski, G. Elmadjian, A. Savov, E. Stoyanova, V. Shivarov, P. Petrov, A. Pashov. 
Restriction of the Global IgM Repertoire in Antiphospholipid Syndrome. Frontiers in Im-munology 13 (2022) 
4. Pashov, A., R. Murali, I. Makhoul, B. Karbassi, T. Kieber-Emmons. 
Harnessing Antibody Polyspecificity for Cancer Immunotherapy. Monoclonal antibodies in immunodiagnosis and immunotherapy 41 (2022) (5),290-300.
5. Kieber-Emmons, T., A. Pashov. 
Living with Endemic COVID-19. Monoclonal antibodies in immunodiagnosis and immuno-therapy 41 (2022) (4),171-172.
6. Pashov, A., R. Murali. 
Should All Memory B Cells Recruited to the Germinal Center Be Antigen Specific? Mon-oclonal antibodies in immunodiagnosis and immunotherapy 40 (2021) (2),50-51.
7. Pashov, A., T. Kieber-Emmons. 
Will a B1.1.1.529 Vaccine Be Undermined by Antigenic Sin: An Idiotypy Inspired Worka-round. Monoclonal antibodies in immunodiagnosis and immunotherapy 40 (2021) (6),237-238.
8. Gorshkova, E. N., S. Pashova, E. A. Vasilenko, T. S. Tchurina, E. A. Razzorenova, O. V. Starkina, P. Dimitrova, A. Pashov, T. L. Vassilev.
 Induced Polyspecificity of Human Secretory Immunoglobulin A Antibodies: Is It Possible to Improve Their Ability to Bind Pathogens? Pharmacology (2021),1-10.
9. Shivarov, V., P. K. Petrov, A. D. Pashov. 
Potential SARS-CoV-2 Preimmune IgM Epitopes. Frontiers in Immunology 11 (2020) (932)
10. Planchais, C., J. Rayes, S. Delignat, S. Pashova, A. Varthaman, A. Pashov, J. Bayry, S. V. Kaveri, J. D. Dimitrov, S. Lacroix-Desmazes. 
Stimulation with FITC-labeled antigens confers B cells with regulatory properties. Cell Immunol 355 (2020) (104151),1-8.
11. Pashov, А., Т. Kieber-Emmons. 
Mimetic Vaccines in Immuno-Oncology. In: Arnouk, H (ed) Cancer Immunotherapy and Biological Cancer Treatments, vol 2019 
12. Pashov, A., V. Shivarov, M. Hadzhieva, V. Kostov, D. Ferdinandov, K.-M. Heintz, S. Pash-ova, M. Todorova, T. Vassilev, T. Kieber-Emmons, L. A. Meza-Zepeda, E. Hovig. 
Diagnostic Profiling of the Human Public IgM Repertoire With Scalable Mimotope Librar-ies. Frontiers in Immunology 10 (2019) (2796),1-14.
13. Kohler, H., A. Pashov, T. Kieber-Emmons. 
The Promise of Anti-idiotype Revisited. Frontiers in Immunology 10 (2019) (808)
14. Vassilev, T. L., V. Kostov, S. von Gunten, A. D. Pashov. 
Basics of Immunoglobulins as Effector Molecules and Drugs. In: Imbach, P (ed) Antibody Therapy: Substitution – Immunomodulation – Monoclonal Immunotherapy, vol 2018  pp 133-150.
15. Pashov, A., C. V. Hernandez Puente, S. M. Ibrahim, B. Monzavi-Karbassi, I. Makhoul, T. Kieber-Emmons. 
Thinking Cancer. Monoclonal antibodies in immunodiagnosis and immunotherapy 37 (2018) (3),117-125.
16. Pashova, S., C. Schneider, S. von Gunten, A. Pashov. 
Antibody repertoire profiling with mimotope arrays. Human vaccines & immunotherapeu-tics 13 (2017) (2),314-322.
17. Murali, R., S. Saha, A. Pashov, T. Kieber-Emmons. 
Summarizing Solvation Effects on Antibody Structure and Function. J Nat Sci 3 (2017) (7),e402.
18. Hadzhieva, M., A. D. Pashov, S. Kaveri, S. Lacroix-Desmazes, H. Mouquet, J. D. Dimitrov. 
Impact of Antigen Density on the Binding Mechanism of IgG Antibodies. Scientific reports 7 (2017) (1),3767.
19. Schneider, C., D. F. Smith, R. D. Cummings, K. F. Boligan, R. G. Hamilton, B. S. Bochner, S. Miescher, H.-U. Simon, A. Pashov, T. Vassilev, S. von Gunten. 
The human IgG anti-carbohydrate repertoire exhibits a universal architecture and con-tains specificity for microbial attachment sites. Science Translational Medicine 7 (2015) (269),269ra261.
20. Saha, S., R. Murali, A. Pashov, T. Kieber-Emmons. 
The Potential Role of Solvation in Antibody Recognition of the Lewis Y Antigen. Monoclo-nal antibodies in immunodiagnosis and immunotherapy 34 (2015) (5),295-302.
21. Garimalla, S., T. Kieber-Emmons, A. D. Pashov. 
The Patterns of Coevolution in Clade B HIV Envelope's N-Glycosylation Sites. PLoS ONE 10 (2015) (6),e0128664.
22. Saha, S., A. Pashov, E. R. Siegel, R. Murali, T. Kieber-Emmons. 
Defining the recognition elements of lewis y-reactive antibodies. PLoS ONE 9 (2014) (8),e104208.
23. Pashov, A. D., T. Calvez, L. Gilardin, B. Maillere, Y. Repesse, J. Oldenburg, A. Pavlova, S. V. Kaveri, S. Lacroix-Desmazes. 
In silico calculated affinity of FVIII-derived peptides for HLA class II alleles predicts inhibi-tor development in haemophilia A patients with missense mutations in the F8 gene. Hae-mophilia 20 (2014) (2),176-184.
24. Djoumerska-Alexieva, I., S. Pashova, T. Vassilev, A. Pashov. 
The protective effect of modified intravenous immunoglobulin in LPS sepsis model is as-sociated with an increased IRA B cells response. Autoimmun Rev 12 (2013) (6),653-656.
25. Dimitrov, J. D., A. Pashov, T. Vassilev. 
Antibody Polyspecificity: What Does It Matter? In: Lutz, HU (ed) Naturally Occurring An-tibodies (NAbs), vol 1 2012  p 268.

Patents related with TOPIC 1

WO2014US49309 20140731/US 61860827: Kieber-Emmons Thomas [USA]; Pashov Anastas [USA]; Karbassi Behjatolah [USA]. Compositions For And Methods Of Treating And Preventing Cancer Targeting Tumor Associated Carbohydrate Antigens.  

BG # 67568/ 05.09.2023 Velizar Stephanov Shivarov,  Anastas Dimitrov Pashov, SARS-CoV-2-Specific B-cell Epitopes.

TOPIC 2 (www.projectimmunolbg.com):

Prof. Petya Dimitrova's team is developing a high-content cellomics platform for drug screening. Her team’s efforts are aimed at applying precise multi-parametric analysis in the study of functional changes in innate immune cells after treatment with molecules of natural origin, low molecular weight inhibitors of histone deacetylases (HDACs), and inhibitors of kinases associated with metabolic signaling pathways and exopolysaccharides. The ultimate goal is to identify new therapeutic agents that target myeloid cells (i.e. neutrophils or granulocytes) and their precursors as a tool for therapeutic intervention in autoimmune diseases and diseases characterized by chronic inflammation and abnormal immune responses, as well as in conditions, associated with immune hyperactivity or immunosuppression. Recently, our research focus is devoted to the characterization of the epigenetic mechanisms (chromatin accessibility dynamics, which lead to changes in gene expression and functional states), activated by protective immunity against respiratory viral infections developing during undelaying chronic inflammation.   

Projects, related to TOPIC 2 

2022-2024: FNI КП-06-М61/6: Study of the effect of cannabidiol in combination with Imatinib on the expression of exosomal and cellular microRNAs in an in vitro model of chronic myeloid leukemia. PI: Dr. Petar Donchev. Stephan Angeloff Institute of Microbiology-Sofia, Bulgaria.

2022-2023: The National Program "Young scientists and postdoctoral fellows-2: : “Bioinformatic transcriptomic analysis of the effect of cannabidiol on the K562 cell line, a model of chronic myeloblastic leukemia”.  PI: Dr. Petar Donchev. Stephan Angeloff Institute of Microbiology-Sofia, Bulgaria.

2020-2023: ACIP, m6A_RAIAV: The lung epitranscriptome and chromatin accessibility landscape in rheumatoid arthritis complicated by the flu. Coordinator: Milena Leseva, Stephan Angeloff Institute of Microbiology-Sofia, Bulgaria; CoPI: Dr. M. Hasan, Institut Pasteur-Paris, France; CoPI: C. Barbezange, Sciensano-Brussels, Belgium. 

ACIP 328-20 aims to characterize the molecular underpinnings of these phenomena and to test the hypothesis that internal mRNA modifications, specifically N6-methyladenosine (m6A), induced by the inflammatory milieu, as well as arthritis-associated cell type-specific changes to chromatin accessibility exacerbate the host immune response and lung tissue damage during the respiratory viral infection. 

2017-2021:  FNI, ДН11/05: Sirtuins (SIRTs) – new targets for fine selective epigenetic regulation of joint inflammation pathology during influenza infection. PI: Assoc. Prof. Petya Dimitrova, Stephan Angeloff Institute of Microbiology-Sofia, Bulgaria; CoPI: Dr. Lora Simeonova, Department of Virology, Institute of Microbiology-Sofia, Bulgaria. 

The project aims to characterize a new therapeutic approach based on the administration of sirtuin activators or inhibitors, as a tool to fine-tune and regulate neutrophil function in chronic inflammation in a model of rheumatoid arthritis, and in acute and moderate influenza infection.

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

The project aims to investigate the role of neutrophils and NK cells in the pathogenesis of osteoarthritis and to direct research towards new approaches to therapy of the disease.

2012 DO2 538/12: Ministry of science, education and youth; EU program Science and Business BG051 PO001/3.3 05 0001: Abrogated RANKL expression in properdin-deficient mice is associated with better outcome from collagen-antibody-induced arthritis. PI: Assoc. Prof. Petya Dimitrova, The Stephan Angeloff Institute of Microbiology-Sofia.

The project aims to prove the relationship between innate immunity (complement) and bone destruction, in the pathogenesis of osteoarthritis and to direct research towards new approaches based on regulation of the alternative pathway of complement activation for disease therapy.

2007-2010 NATO/EAG.RIG 982937/2007: Prevention of shock and multiple organ dysfunction by protein kinase inhibitor tyrphostin, PI: Assoc. Prof. Petya Dimitrova, The Stephan Angeloff Institute of Microbiology-Sofia, Bulgaria.

The project aims to investigate the action of inhibitors of the JAK/STAT signaling pathway as a novel approach for therapy in systemic inflammatory response and septic shock. 

2007-2010 NSF/POST-DOC 1005/07: Role of acute phase proteins in septic shock induced by Candida albicans. PI: Assoc. Prof. Petya Dimitrova, The Stephan Angeloff Institute of Microbiology-Sofia, Bulgaria.

The project aims to identify new diagnostic markers for rapid monitoring of the immune response in systemic inflammatory response and septic shock.

2020-2023: ACIP, m6A_RAIAV: The lung epitranscriptome and chromatin accessibility landscape 

Awards

2018: Assist. Prof. Milena Leseva: EMBL Corporate Partnership Programme fellowship

2017: Assoc. Prof. Petya Dimitrova: Fulbright Visiting Scholar Grant: Mentor Prof. Jennifer Jane Westendorf Lab of Regenerative Medicine, Department of Orthopedic Surgery, Mayo Clinic, Roch-ester, MN, USA.

2008-2011 Milena Leseva: International Fulbright Science & Technology Award (for studies in the Molecular Cell Biology doctoral program at University of Florida, Gainesville, FL, USA)

2008-2011 Milena Leseva: Grinter Fellowship (incentive for recruiting exceptional PhD students - University of Florida, Gainesville, FL, USA)

Рublications related to TOPIC 2

1. Leseva, M.N., Buttari, B., Saso, L., Dimitrova, P.A. Infection Meets Inflammation: N6-Methyladenosine, an Internal Messenger RNA Modification as a Tool for Pharmacological Regula-tion of Host–Pathogen Interactions. Biomolecules (Special Issue: Advances in RNA as Diagnostic Biomarkers), MDPI, 2023, ISSN:2218-273X, DOI:doi: 10.3390/biom13071060, SJR (Scopus):1.07, JCR-IF (Web of Science):5.5
2. Amirova, K.M., Dimitrova, P.A., Leseva, M.N., Koycheva, I.K., Dinkova-Kostova, A.T., Georgiev, M.I. The triterpenoid Nrf2 activator, CDDO-Me, decreases neutrophil senescence in a murine model of joint damage. International Journal of Molecular Sciences, 24, 10, MDPI, 2023, ISSN:1422-0067, DOI:10.3390/ijms24108775, 8775. JCR-IF (Web of Science):5.6
3. Rusinova-Videva, S. V., Ognyanov, M, Georgiev, Y, Petrova, A, Dimitrova, P, Kambourova, M. Chemical characterization and biological effect of exopolysaccharides synthesized by Antarctic yeasts Cystobasidium ongulense AL101 and Leucosporidium yakuticum AL102 on murine innate immune cells. World Journal of Microbiology and Biotechnology, 39, 2023, DOI:doi.org/10.1007/s11274-022-03477-0, JCR-IF (Web of Science):4.253
4. Simeonova L., Gegova G., Doumanova L., Kaleva A., Leseva M., Dimitrova P. Host Epigenetic Mechanisms In Experimental Anti-Influenza Therapy. Modern Microbiology: A Challenge For Im-proving The Quality Of LIfe. 75th Anniversary of the Stephan Angeloff Institute of Microbiology, Farrago, 2022, ISBN:978-619-206-207-1, 212-219
5. Amirova, K.M., Dimitrova, P.A., Marchev, A.S., Krustanova, S., Simova, S., Alipieva, K., Georgiev, M.I. Biotechnologically-produced myconoside and calceolarioside E induce Nrf2-expression in neu-trophils. International Journal of Molecular Sciences, 22, 4, MDPI, 2021, ISSN:1422-0067, DOI:10.3390/ijms22041759, 1759. SJR (Scopus):1.455, JCR-IF (Web of Science):6.208
6. 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)
7. Leseva, M, Binder, AM, Ponsonby, AL, Vuillermin, P, Saffery, R, Michels, KB, BIS Investigator Group. Differential gene expression and limited epigenetic dysregulation at the maternal-fetal in-terface 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)
8. 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)
9. 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 activa-tion. 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)
10. 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 Individu-als. 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)
11. 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 prolifera-tion. 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)
12. 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, HU, 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)
13. Benigni, G, Dimitrova, P, Antonangeli, F, Sanseviero, E, Milanova, V, Blom, A, van Lent, P, Mor-rone, 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, Amer-ican Association of Immunologists, 2017, ISSN:0022-1767, DOI:10.4049/jimmunol.1601359, 2115-2124. SJR (Scopus):3.368, JCR-IF (Web of Science):4.539 Q1 (Scopus)
14. 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)
15. 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)
16. Donchev P, Kaloyanov K, Yotova М, Momekov G, Konstantinov S. Exosomes in CML development and progression. PHARMACIA, 64, 4, 2017, SJR (Scopus):0.11
17. Kaloyanov K, Donchev P, Yotova, M, Momekov G, Konstantinov, S. Different type of cell death induction by curcumin, arsenic trioxide and degrasyn (wp1130) in human multiple myeloma cells. International Journal of Pharmaceutical Sciences and Research. 2017, 2893-2899. 10.13040/IJPSR.0975-8232.8(7).2893-99. 

TOPIC 3 (www.projectimmunolbg.com):

Prof. Dr. Tchavdar Vassilev together with Assoc. Prof. Anastas Pashov and Assoc. Prof. Petya Dimitrova developed the research in the field of immunoglobulin reactivity. Prof. Dr. Tchavdar Vassilev is a leader in research into the immunoregulatory properties of intravenous immunoglobulin preparations. The team is recognized for its competences and discoveries in the field of induced polyspecificity of antibodies and especially for the impressive results in the experimental therapy of sepsis with modified immunoglobulin preparations.

Projects related to TOPIC 3

2019-2021: FNI, KP-06-Russia-5. Polyspecificity of immunoglobulin A and G. PI: Prof. Petya Dimitrova, CoPI: Dr. Ekaterina Gorshkova, Lobachevski State University of Nizhni Novgorod, Russia.

2015-2021: FNI, DB 02-29: The physiological role and therapeutic potential of antibodies with induced polyspecificity. PI: Prof. Tchavdar Vassilev.

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

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.

Статии в направление 3:

1. Gorshkova, EN, Lecerf, M, Astrakhantseva, IV, Vasilenko, EA, Starkina, OV, Ilyukina, NA, Dimitrova, PA, Dimitrov, JD, Vassilev, TV. Induced antigen-binding polyreactivity in human serum IgA. Immunobiology, 227, 3, Urban und Fischer Verlag GmbH und Co. KG, 2022, ISSN:0171-2985, DOI:doi.org/10.1016/j.imbio.2022.152213, 152213. SJR (Scopus):0.709, JCR-IF (Web of Science):3.152
2. Gorshkova E.N., Pashova S., Vasilenko E.A., Tchurina T.S., Razzorenova E.A., Starkina O.V., Dimitrova P., Pashov A., Vassilev T.. Induced polyspecificity of human secretory IgA antibodies: Is it possible to improve their ability to bind pathogens?. Pharmacology, S. Karger AG, 2021, DOI:10.1159/000520343, SJR (Scopus):0.51, JCR-IF (Web of Science):2.547
3. Graeter S, Schneider C, Verschoor D, von Däniken S, Seibold F, Yawalkar N, Villiger P, Dimitrov JD, Smith DF, Cummings RD, Simon HU, Vassilev T, von Gunten S. Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils. Front Immunol., 19, 11, Frontiers Media S.A., 2020, ISSN:16643224, DOI:10.3389/fimmu.2020.00973, 973. SJR (Scopus):2.646, JCR-IF (Web of Science):7.972
4. Vassilev, TL, Kostov, V, von Gunten, V., Pashov, AD. 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
5. 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, no tops the rankings (Web of Science)
6. Djoumerska-Alexieva, I, Stefanova, T, Vassilev, T, Roumenina, LT, Dimitrov, JD 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)
7. 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, JM, 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 Q1 (Scopus)
8. Hadzhieva, M., Vassilev, T., Bayry J, Kaveri S, Lacroix-Desmazes S, Dimitrov JD. Relationship between natural and heme-mediated antibody polyreactivity.. Biochem Biophys Res Commun., 472, 1, 2016, 281-286. SJR (Scopus):1.18, JCR-IF (Web of Science):2.371

Patents related with TOPIC 3

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). T.L. Vassilev, J.D. Approach For Increasing Antigen-Binding Activity Of Immuno-Globulin Preparations.