Immunology and Neuroimmunology

Prof. RNDr. Eva Kontseková, DSc

Neuroimmunology The Laboratory of Immunology and Neuroimmunology is focused on understanding the mechanisms of neuro-immune interactions in Alzheimer´s disease and other neurodegenerative diseases.

We use transgenic animal models to study the interactions between the immune and nervous systems that are affected by the neurodegenerative process. We explore the impact of neurodegeneration on the immune system, develop immunotherapeutic approaches, and analyse their effectiveness with emphasis on the understanding of the molecular mode of action. At present, the group is dedicated to the interpretation of the neuro-immune mechanisms acting at the origin and development of Alzheimer’s disease and other neurodegenerations.

The group has a long tradition in the development of monoclonal antibodies against a wide range of proteins. We have generated many antibodies that recognize the critical antigenic determinants of the pathological forms of the neuronal protein tau, which is the key player in the pathophysiology of Alzheimer’s disease. These antibodies helped us to uncover a therapeutic target for pathological tau protein. The antibodies also serve as sensitive tools for the study of the structure-function relationship of intrinsically disordered proteins like tau.

Our experience facilitated the development of antibodies that neutralize all emerged variants of SARS-CoV-2, the coronavirus that caused the COVID-19 pandemic.

The Laboratory has been investigating the immune response induced by vaccinations for many years. We exploit our experience to identify differences in how human adaptive immunity reacts to the infection by SARS-CoV-2 and to the vaccination. Our aim is to define the critical components of the adaptive immunity, which are needed for the development of effective strategies to control and prevent viral infections.

The laboratory is equipped with a complete setup for proteomic and molecular biology analyses and a dedicated facility for cell and tissue culture research and flow cytometry.

Lab members

  • MSc. Branislav Kováčech, PhD
  • Ľubica Fialová, DVM, PhD
  • RNDr. Monika Žilková, PhD
  • Ing. Gabriela Paulíková Roľková, PhD
  • Ing. Natália Turic Csóková, PhD
  • MSc. Ľubica Wojčiaková
  • MSc. Karina Marková
  • Jana Síthová (technician)

Projects – funding

  • APVV-20-0585 (1.7.2021-30.6.2025)
  • Neuro-glia cell-based model for inter-neuronal spread of tau pathology
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  • VEGA 2/0154/22 (1.1.2022-31.12.2024)
  • The effect of glial cells on tau spreading in neuro-glia cell-based model for Alzheimer’s disease
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  • APVV-21-0478 (1.7.2022-30.6.2025) Longitudinal monitoring of adaptive immunity after SARS-CoV -2 infection and vaccination: markers of immunity

Selected Publications

Kovacech B, Fialova L, Filipcik P, Skrabana R, Zilkova M, Paulenka-Ivanovova N, Kovac A, Palova D, Paulíkova Rolkova D, Tomkova K, Turic Csokova N, Markova K, Skrabanova M, Sinska K, Basheer N, Majerova P, Hanes J, Parrak V, Prcina M, Cehlar O, Cente M, Piestansky J, Fresser M, Novak M, Slavikova M, Borsova K, Cabanova V, Brejova B, Vinař T, Nosek J, Klempa B, Zilka N, Kontsekova E. 2021. Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern. EBioMedicine, 2022 Feb; 76:103818.

Novak P, Kovacech B, Katina S, Schmidt R, Scheltens F, Kontsekova E, Ropele S, Fialova L, Kramberger M, Paulenka-Ivanovova N, Smisek M, Hanes J, Stevens E, Kovac A, Sutovsky S, Parrak V, Koson P, Prcina M, Galba J, Cente M, Hromadka T, Filipcik P, Piestansky J, Samcova M, Prenn-Gologranc C, Sivak R, Froelich L, Fresser M, Rakusa M, Harrison j, Hort J, Otto M, Tosun D, Ondrus M, Winblad B, Novak M, Zilka N. ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease. Nature Aging, 2021 June; 1:521–534.

Murgoci A-N, Duhamel M, Raffo-Romero A, Mallah K, Aboulouard S, Lefebvre C, Kobeissy F, Fournier I., Zilkova M., Maderova D., Cizek M., Cizkova D and Salzet, M. Location of neonatal microglia drives small extracellular vesicles content and biological functions in vitro. J Extracell Vesicles, 2020;9 (1).

Zilkova, M., Nolle, A., Kovacech, B., Kontsekova, E., Weisova, P., Filipcik,P., Skrabana, R., Prcina, M., Hromadka, T., Cehlar, O., Paulikova Rolkova, G., 1, Maderova, D., Novak,M., Zilka, N Hoozemans, JJM. Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation. Acta Neuropathol Commun, 2020, 8:74.

Weisova, P., Cehlar, O., Skrabana, R., Zilkova, M., Filipcik, P., Kovacech, B., Prcina, M., Wojciakova, L., Fialova, L., Smolek, T., Kontsekova, E., Zilka, N., Novak, M. Therapeutic antibody targeting microtubule-binding domain prevents neuronal internalization of extracellular tau via masking neuron surface proteoglycans. Acta Neuropathol Commun, 2019, 7:129.

Jadhav S, Avila J, Schöll M, Kovacs GG, Kövari E, Skrabana R, Evans LD, Kontsekova E, Malawska B, de Silva R, Buee L, Zilka N. A walk through tau therapeutic strategies. Acta Neuropathol Commun, 2019 Feb 15;7(1):22.

Novak P, Zilka N, Zilkova M, Kovacech B, Skrabana R, Ondrus M, Fialova L, Kontsekova E, Otto M, Novak M. AADvac1, an Active Immunotherapy for Alzheimer’s Disease and Non Alzheimer Tauopathies: An Overview of Preclinical and Clinical Development. J Prev Alzheimers Dis, 2019;6(1):63-69.

Novak P, Kontsekova E, Zilka N, Novak M. Ten Years of Tau-Targeted Immunotherapy: The Path Walked and the Roads Ahead. Front Neurosci, 2018 Nov;12.

Novak P, Schmidt R, Kontsekova E, Kovacech B, Smolek T, Katina S, Fialova L, Prcina M, Parrak V, Dal-Bianco P, Brunner M, Staffen W, Rainer M, Ondrus M, Ropele S, Smisek M, Sivak R, Zilka N, Winblad B, Novak M. FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer’s disease. Alzheimers Res Ther, 2018 Oct 24;10(1):108.

Novak P, Schmidt R, Kontsekova E, Zilka N, Kovacech B, Skrabana R, Vince-Kazmerova Z, Katina S, Fialova L, Prcina M, Parrak V, Dal-Bianco P, Brunner M, Staffen W, Rainer M, Ondrus M, Ropele S, Smisek M, Sivak R, Winblad B, Novak M. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol, 2017 Feb;16(2):123-134.

Paholikova K, Salingova B, Opattova A, Skrabana R, Majerova P, Zilka N, Kovacech B, Zilkova M, Barath P, Novak M. 2015. N-terminal Truncation of Microtubule Associated Protein Tau Dysregulates its Cellular Localization. J Alzheimers Dis, 1;43(3):915-26. doi: 10.3233/JAD-140996

Prcina, M.; Kontsekova, E.; Novak, M. 2015. Prion protein prevents heavy metals overloading of cells and thus protects them against their toxicity. Acta Virologica, 59: 179-184

Kontseková E, Žilka N, Kováčech B, Novák P, Novák M. 2014. First-in-man tau vaccine targeting structural determinants essential for pathological tau–tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer’s disease model. Alzheimer’s Research & Therapy, 6: 44.

Kontseková E, Žilka N, Kováčech B, Škrabana R, Novák M. 2014. Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease. Alzheimer’s Research & Therapy, 6: 45.

Majerova P, Zilkova M, Kazmerova Z, Kovac A, Paholikova K, Kovacech B, Zilka N, Novak M. 2014. Microglia display modest phagocytic capacity for extracellular tau oligomers. J Neuroinflammation, Sep 13;11(1):161

Kazmerova Z, Zilka N, Cente M, Neradil P, Zilkova M, Novak M. Can We Teach Old Dogs New Tricks? 2013. Neuroprotective Cell Therapy in Alzheimer’s and Parkinson’s Disease. J Alzheimers Dis, 37: 251-272

Žilka N, Kováčech B, Baráth P, Kontseková E, Novák M. 2012. The self-perpetuating tau truncation circle. Biochemical society transactions, 40, no.4: 681-686.

Novak P, Prcina M, Kontsekova E. 2011. Tauons and prions-infamous cousins? J Alzheimers Dis, 26 (3): 413-430

Prčina, M., Kontseková, E. 2011. Has prion protein important physiological function? Medical Hypotheses, 76: 567–569

Zilkova M, Zilka N, Kovac A, Kovacech B, Skrabana R, Skrabanova M, Novak M. 2011. Hyperphosphorylated truncated protein tau induces caspase-3 independent apoptosis-like pathway in the Alzheimer’s Disease cellular model. J Alzheimers Dis, 23: 161-U173.

Zilka N, Zilkova M, Kazmerova Z, Sarissky M, Cigankova V, Novak M. 2011. Mesenchymal stem cells rescue the alzheimer’s disease cell model from cell death induced by misfolded truncated tau. Neuroscience, 193: 330-337.

Novak P, Prcina M, Kontsekova E. 2011. Tauons and Prions: Infamous Cousins? J Alzheimers Dis, 26: 413-430