ennshapkabg
 

Celebration 67 years The Stephan Angeloff Institute of Microbiology

 

Microbiologia Balkanica 2013 - 8th Balkan Congress of Microbiology, Veliko Tarnovo, Bulgaria

 

Pitagor 2012 awarded to Assoc. Prof. Andrey Tchorbanov from The Stephan Angeloff Institute of Microbiology

 

Meeting of the President of BAS prof. Nikola Sabotinov with Dr. Mark Jouan from RIIP

 

Official ceremony of Academic degrees diploma awards

 

Pitagor 2011 awarded to two researchers from The Stephan Angeloff Institute of Microbiology

 

 

Закон за развитие на академичния състав в Република България

 

 

Правилник за прилагане на Закона за развит на академичния състав в Република България

 

 

Процедури по закона за развитие на академичния състав в Република България

 

 

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Bulgarian Academy of Sciences

 

Ministry of Education and Science

 

National Science Fund

 

Central Library of BAS

 

Union of Scientists in Bulgaria

 

European
Comission: Horizon 2020

Institut Pasteur

 

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LABORATORY of Experimental Immunotherapy

 

Head: Associate Professor Anastas Pashov, PhD

е-mail: a_pashov@microbio.bas.bg

 

Tel: +359 2 979 6348

 

 Staff

 

Prof. Tchavdar Vassilev, M.D., Ph.D., vassilev@microbio.bas.bg

 

Assoc. Prof. Petya Dimtrova, Ph.D., petya_dimitrova@web.de

 

Assistant Prof. Iglika Djoumerska-Alexieva. M.D., Ph.D., djoumer@microbio.bas.bg

 

PhD Student Maya Hadjieva

 

 

Contacts: +359 2 979 6348,  +359 2 979 3140, +359 2 979 6357

 

 

Main Research topics


  • Novel immunotherapeutics based on intravenous immunoglobulins

  • Immunotherapy of sepsis,

  • Immunotherapy of inflammatory and degenerative tissue damage,

  • Immunogenicity of biopharmaceuticals,

  • Development of biomarkers based on system analysis of the antibody repertoire

     

    Projects

     

  • 2015-2017 National Fund “Scientific Research”. B 02/275 Physiological role and therapeutic potential of antibodies with induced polyspecificity. PI: Prof. Tchavdar Vassilev

  • 2012-2015 SNSF IZEBZO_142967: Design of modified immunoglobuin 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

  • 2007-2013: BG 051 PO001-3.3.04/32: Operational Programme "Human Resources Development", co-financed by the European Social Fund of the European Union: Effective training of students and career development of post-docs and young researchers in priority areas of microbiology”. Lector in the Module Immunology: PI: Assoc. Prof. Petya Dimitrova

  • 2010-2013 Marie Curie International Re-integration Grants (IRG), FP7-PEOPLE-2009-RG 248289. 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, Co-PI: Prof. Angela Santoni University La Sapienza-Rome, Co-PI: Crina Stavaru, Cantacuzino Institute-Bucharest.

  • 2012: DО2 538/20.06.2012 - Ministry of Science, Youth and Education Program: BG051 PO001/3.3 05 0001 “Science and Business”, Support of specialized publications in refereed journals with impact factor: Abrogated RANKL expression in properdin-deficient mice is associated with better outcome from collagen-antibody-induced arthritis). PI: Assoc. Prof. Petya Dimitrova. 

 

Most Important results

 

 

    • Using a method for modification of IgG specificity patented by us, we developed a pooled human immunoglobulin preparation for intravenous use with an enhanced anti-inflammatory effect. Unlike the commercial preparations (IVIg), their modified variants exert a powerful immunotherapeutic effect in sepsis models. The mechanisms of action of the modified IVIg cannot be reduced to individual antibody specificity, antibacterial action, a single factor or isolated signaling path. Instead, our studies showed multiple effects including increased reactivity with some cytokines, complement components, molecular structures recognized as “danger signals”, etc. Thus, the effect of modified IVIg is better characterized as systemic and seems to offer a model, the studies on which could outline a new system immunology paradigm. It would trigger the development of a new class of immunotherapies related to the fast growing field of the system biology and, probably, offer a novel and efficient strategy for the treatment of sepsis.

    • Applying a system biology approach to the antibody repertoire studies, we develop diagnostic methods based on the signatures in a large number of antibody reactivities (103- 104) used as biomarkers in a broad nosology spectrum. To this end, microarrays are designed, which contain 4000 -10000 diverse peptides selected among known B cell epitopes together with their homologues, diversified according an in house bioinformatic algorithms, as well as complete library of tripeptides in a pharmacophore like analysis.

    • Studying the approaches to alter functions of neutrophils and their interaction with immune or tissue-specific cells as a tool for tissue repair modulation in a variety of pathologies and disorders.

    • Bioinformatic algorithms are being developed for the prediction of the risk of inhibitory anti-drug antibody elicitation during treatment with biopharmaceuticals. Factor VIII of the coagulation cascade was used as a model whereby the immunogenicity of the protein is considered in the context of the HLA haplotype of the patient. The design of another algorithm for “deimmunization” of biopharmaceuticals is ongoing too. It is based on mutations that destroy the immunogenic epitopes but preserve the function.

    • In a study on the capacity of different B cell populations in the mouse to modify the phenotype of co-stimulated T cells a potential regulatory role was found for the T1 splenic B cell population as well as for the B cells with polyspecific B cell receptor after suboptimal stimulation with broadly cross-reacting epitope - fluorescein. A correlation was found between the immunotherapeutic effects of the modified immunoglobulins and the stimulation of B celss with the phenotype of plasmablasts from the B1 population (allegedly innate response activators secreting GM-CSF)




Selected  Publications



  • Von Gunten S, Shoenfeld Y, Blank M, Branch DR, Vassilev T, Käsermann F, Bayry J, Kaveri S, Simon HU. 2014,IVIG pluripotency and the concept of Fc-sialylation: challenges to the scientist. Nature Rev.Immunol,14, 349-350.

  • Pavlovic, S., Zdravkovic, N., Peijnovic, N., Djoumerska-Alexieva, I., Arsenjevic, N., Vassilev, T., Lukic, M. Enhanced anti-diabetogenic effect of intreavenous immune globulin modified by ferrous ion exposure. Eur.J.Inflamm. 2014: 12, 67-76, ISSN 1721-727X

  • Lecerf M, Scheel T, Pashov AD, Jarossay A, Ohayon D, Planchais C, Mesnage S, Berek C, Kaveri SV, Lacroix-Desmazes S, Dimitrov JD. 2015. Prevalence and Gene Characteristics of Antibodies with Cofactor-induced HIV-1 Specificity. Journal of Biological Chemistry

  • Schneider C, Smith DF, Cummings RD, Boligan KF, Hamilton RG, Bochner BS, Miescher S, Simon H-U, Pashov A, Vassilev T, von Gunten S. 2015. The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites. Science Translational Medicine 7: 269ra1

  • Kieber-Emmons T, Saha S, Pashov A, Monzavi-Karbassi B, Murali R. 2014. Carbohydrate-mimetic peptides for pan anti-tumor responses. Front Immunol 5: 308

  • Saha S, Pashov A, Siegel ER, Murali R, Kieber-Emmons T. 2014. Defining the recognition elements of lewis y-reactive antibodies. PLoS One 9: e104208

  • Pashova S, Dobrev K, Pashov A. 2014. Rregulatory Properties of Mouse Transitional 1 B Lymphocytes. Comptes rendus de l'Academie bulgare des Sciences 67: 361-6

  • Marinozzi MC, Vergoz L, Rybkine T, Ngo S, Bettoni S, Pashov A, Cayla M, Tabarin F, Jablonski M, Hue C, Smith RJ, Noris M, Halbwachs-Mecarelli L, Donadelli R, Fremeaux-Bacchi V, Roumenina LT. 2014. Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign? J Am Soc Nephrol 25: 2053-65

  • Pashov AD, Calvez T, Gilardin L, Maillere B, Repesse Y, Oldenburg J, Pavlova A, Kaveri SV, Lacroix-Desmazes S. 2014. In silico calculated affinity of FVIII-derived peptides for HLA class II alleles predicts inhibitor development in haemophilia A patients with missense mutations in the F8 gene. Haemophilia 20: 176-84

  • Monzavi-Karbassi B, Pashov A, Kieber-Emmons T. 2013. Tumor-Associated Glycans and Immune Surveillance. Vaccines 1: 174-203

  • Djoumerska-Alexieva I, Pashova S, Vassilev T, Pashov A. 2013. The protective effect of modified intravenous immunoglobulin in LPS sepsis model is associated with an increased IRA B cells response. Autoimmun Rev 12: 653-6

  • Kieber-Emmons T, Monzavi-Karbassi B, Pashov A, Saha S, Murali R, Kohler H. 2012. The promise of the anti-idiotype concept. Front Oncol 2: 196

  • Hennings L, Artaud C, Jousheghany F, Monzavi-Karbassi B, Pashov A, Kieber-Emmons T. 2011. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology. Cancers 3: 4151-69

  • Pashov A, Delignat S, Bayry J, Kaveri SV. 2011. Enhancement of the Affinity of Glucocorticoid Receptors as a Mechanism Underlying the Steroid-sparing Effect of Intravenous Immunoglobulin. The Journal of Rheumatology 38: 2275

  • Pashov A, Monzavi-Karbassi B, Raghava GP, Kieber-Emmons T. 2010. Bridging innate and adaptive antitumor immunity targeting glycans. J Biomed Biotechnol 2010: 354068

  • Pashov A, Monzavi-Karbassi B, Kieber-Emmons T. 2011. Glycan mediated immune responses to tumor cells. Hum Vaccin 7: 156-65

  • Pashov A, Garimalla S, Monzavi-Karbassi B, Kieber-Emmons T. 2009. Carbohydrate targets in HIV vaccine research: lessons from failures. Immunotherapy 1: 777-94

  • Dimitrov JD, Planchais C, Kang J, Pashov A, Vassilev TL, Kaveri SV, Lacroix-Desmazes S. 2010. Heterogeneous antigen recognition behavior of induced polyspecific antibodies. Biochemical and Biophysical Research Communications 398: 266-71

  • Todorova VK, Klimberg VS, Hennings L, Kieber-Emmons T, Pashov A. 2010. Immunomodulatory effects of radiofrequency ablation in a breast cancer model. Immunol Invest 39: 74-92