Research areas
The main research topics at the Dept. of Immunology are: development of monoclonal and recombinant antibodies, investigation of recombinant viral antigens, prevalence studies of viral infections (A. Žvirblienė, I. Kučinskaitė-Kodzė, M. Simanavičius, D. Stravinskienė), studies on bacterial virulence factors (M. Plečkaitytė), studies on the molecular mechanisms of macrophage activation (A. Lučiūnaitė, I. Dalgėdienė).
Modern facilities for cell culture work, immunoassays, microscopy, flow cytometry, molecular biology experiments are available.
Antibody development and research
Our team has extensive expertise in the development and characterization of monoclonal and recombinant antibodies. We have generated large collections of monoclonal antibodies against different targets: viral antigens, bacterial virulence factors, cellular proteins, cytokines, hormones, allergens. The largest antibody collection is generated against viral antigens. These antibodies are valuable tools for investigating the antigenic structure of viruses, development of diagnostic assays and studying the prevalence of viral infections.
For the construction of recombinant antibodies, gene sequences encoding the variable parts of immunoglobulin heavy and light chains are cloned from hybridoma cells producing well-characterized monoclonal antibodies against the target of interest. Recombinant antibodies are developed in different formats: as single chain antibodies (scFv) and Fc-engineered antibodies, where the scFv derived from hybridoma cells are joined to the human IgG Fc fragment. In addition, we have exploited recombinant virus-like particles as carriers for antibody molecules, both scFv and Fc-engineered scFv. This innovative approach allows the generation of recombinant multimeric antibodies displayed on virus-like particles.
Our research team is a member of the international network EuroMabNet, collaborates with academic and industrial partners from Germany, UK, USA, Australia, Finland.
Diagnostics and prevalence studies of viral infections
Our team develops molecular and immunological methods for the detection of various viruses, including zoonotic viruses. Using molecular and serological methods, studies of the prevalence of human hepatitis E virus (HEV) in Lithuania were carried out. In collaboration with Lithuanian biotech companies, our researchers have contributed to the development of serological tests for the detection of antibodies against SARS-CoV-2. During the COVID-19 pandemic, these tests have been employed to investigate the duration of humoral immune response after SARS-CoV-2 infection. Large collections of monoclonal antibodies against the structural proteins of SARS-CoV-2 have been developed and used for studying their antigenic properties. Together with colleagues from Santaros klinikos and the Lithuanian University of Health Sciences, the seroepidemiological study of COVID-19 was performed in spring 2023, that demonstrated a high level of seropositivity against SARS-CoV-2 antigens in the Lithuanian population.
Studies on bacterial virulence factors
Some bacteria produce toxins, cholesterol-dependent cytolysins, which damage human cells by forming pores in their membranes. A large collection of recombinant cytolysins and their specific antibodies have been developed at our department and used to investigate structural and functional properties of cytolysins. The research group led by Dr M.Plečkaitytė investigates the virulence factors of bacterium Gardnerella spp, their mechanisms of action. In collaboration with researchers from Santaros klinikos, this research group also performs molecular and genetic studies of Neisseria meningitides including the coverage of circulating N.meningitidis strains by the currently available vaccines.
Studies on molecular mechanisms of innate immune response to oligomeric antigens
The research group led by Dr A.Lučiūnaitė investigates the mechanisms of activation of innate immune cells by oligomeric antigens of different origin and structure, including viral antigens, using cell lines and primary cultures; activation of macrophages with oligomeric antigens and their immune complexes is studied by evaluating changes in cell viability, the level of secretion of inflammatory cytokines, activation of the NLRP3 inflammasome and other indicators. The activation profile of single cells is also investigated. These studies demonstrate that structural features of the antigens and their immune complexes can determine the profile of the inflammatory response of macrophages.
Publications
2024
Simanavičius M, Kučinskaitė-Kodzė I, Kaselienė S, Sauliūnė S, Gudas D, Jančorienė L, Jasinskienė R, Vitkauskienė A, Žūtautienė R, Žvirblienė A, Stankūnas M. Prevalence of SARS-CoV-2-specific antibodies in a sample of the Lithuanian population-based study in Spring 2023. Heliyon. 2024 Apr 12;10(8):e29343. doi: 10.1016/j.heliyon.2024.e29343.
Lučiūnaitė A, Mašalaitė K, Plikusiene I, Maciulis V, Juciute S, Norkienė M, Žvirblienė A.
Structural properties of immune complexes formed by viral antigens and specific antibodies shape the inflammatory response of macrophages. Cell Biosci. 2024 Apr 25;14(1):53. doi: 10.1186/s13578-024-01237-1.
Rudokas V, Silimavicius L, Kucinskaite-Kodze I, Sliziene A, Pleckaityte M, Zvirbliene A.
Novel monoclonal antibodies against house dust mite allergen Der p 21 and their application to analyze allergen extracts. PeerJ. 2024 Apr 18;12:e17233. doi: 10.7717/peerj.17233
Inciuraite R, Ramonaite R, Kupcinskas J, Dalgediene I, Kulokiene U, Kiudelis V, Varkalaite G, Zvirbliene A, Jonaitis LV, Kiudelis G, Franke A, Schreiber S, Juzenas S, Skieceviciene J. The microRNA expression in crypt-top and crypt-bottom colonic epithelial cell populations demonstrates cell-type specificity and correlates with endoscopic activity in ulcerative colitis. .J Crohns Colitis. 2024 Jul 18:jjae108. doi: 10.1093/ecco-jcc/jjae108
Khatmi G, Klinavičius T, Simanavičius M, Silimavičius L, Tamulevičienė A, Rimkutė A, Kučinskaitė-Kodzė I, Gylys G, Tamulevičius T. Lateral flow assay sensitivity and signal enhancement via laser µ-machined constrains in nitrocellulose membrane. Sci Rep. 2024 Oct 2;14(1):22936. doi: 10.1038/s41598-024-74407-3.
Mačionienė E, Simanavičius M, Vitkauskaitė M, Vickienė A, Staučė R, Vinikovas A, Miglinas M. Urinary Chemokines CXCL9 and CXCL10 Are Non-Invasive Biomarkers of Kidney Transplant Rejection. Ann Transplant. 2024 Oct 15;29:e944762. doi: 10.12659/AOT.944762.
Liustrovaite V, Drobysh M, Ratautaite V, Ramanaviciene A, Rimkute A, Simanavicius M, Dalgediene I, Kucinskaite-Kodze I, Plikusiene I, Chen CF, Viter R, Ramanavicius A. Electrochemical biosensor for the evaluation of monoclonal antibodies targeting the N protein of SARS-CoV-2 virus. Sci Total Environ. 2024 May 10;924:171042. doi: 10.1016/j.scitotenv.2024.171042.
Drobysh M, Liustrovaite V, Kanetski Y, Brasiunas B, Zvirbliene A, Rimkute A, Gudas D, Kucinskaite-Kodze I, Simanavicius M, Ramanavicius S, Slibinskas R, Ciplys E, Plikusiene I, Ramanavicius A. Electrochemical biosensing based comparative study of monoclonal antibodies against SARS-CoV-2 nucleocapsid protein. Sci Total Environ. 2024 Jan 15;908:168154. doi: 10.1016/j.scitotenv.2023.168154.
2023
Ivaškevičienė I, Silickaitė J, Mačionienė A, Ivaškevičius R, Bulavaitė A, Gėgžna V, Kiverytė S, Paškevič B, Žvirblienė A, Plečkaitytė M. Molecular characteristics of Neisseria meningitidis carriage strains in university students in Lithuania. BMC Microbiol. 2023; 23(1):352. doi: 10.1186/s12866-023-03111-5.
Drobysh M, Liustrovaite V, Kanetski Y, Brasiunas B, Zvirbliene A, Rimkute A, Gudas D, Kucinskaite-Kodze I, Simanavicius M, Ramanavicius S, Slibinskas R, Ciplys E, Plikusiene I, Ramanavicius A. Electrochemical biosensing based comparative study of monoclonal antibodies against SARS-CoV-2 nucleocapsid protein.Sci Total Environ. 2023; 908:168154. doi: 10.1016/j.scitotenv.2023.168154.
Lučiūnaitė A, Dalgėdienė I, Vasiliūnaitė E, Norkienė M, Kučinskaitė-Kodzė I, Žvirblienė A, Gedvilaitė A. Immunogenic Properties and Antigenic Similarity of Virus-like Particles Derived from Human Polyomaviruses. Int J Mol Sci. 2023; 24(5):4907. doi: 10.3390/ijms24054907.
Sereikaitė E, Plepytė R, Petrutienė A, Stravinskienė D, Kučinskaitė-Kodzė I, Gėgžna V, Ivaškevičienė I, Žvirblienė A, Plečkaitytė M. Molecular characterization of invasive Neisseria meningitidis isolates collected in Lithuania (2009-2019) and estimation of serogroup B meningococcal vaccine 4CMenB and MenB-Fhbp coverage.Front Cell Infect Microbiol. 2023; 13:1136211. doi: 10.3389/fcimb.2023.1136211
Avižinienė A, Kučinskaitė-Kodzė I, Petraitytė-Burneikienė R, Žvirblienė A, Mertens ML, Schmidt S, Schlegel M, Lattwein E, Koellner B, Ulrich RG. Characterization of a Panel of Cross-Reactive Hantavirus Nucleocapsid Protein-Specific Monoclonal Antibodies.Viruses. 2023;15(2): 532. doi: 10.3390/v15020532.
Sližienė A, Plečkaitytė M, Rudokas V, Juškaitė K, Žvirblis G, Žvirblienė A.
Cross-reactive monoclonal antibodies against fish parvalbumins as a tool for studying antigenic similarity of different parvalbumins and analysis of fish extracts.Mol Immunol. 2023;154: 80-95. doi: 10.1016/j.molimm.2023.01.001
Bakuła Z, Dziurzyński M, Decewicz P, Bakonytė D, Vasiliauskaitė L, Nakčerienė B, Krenke R, Stakėnas P, Jagielski T. Spoligotyping of Mycobacterium tuberculosis - Comparing in vitro and in silico approaches.Infect Genet Evol. 2023; 115:105508. doi: 10.1016/j.meegid.2023.105508.
Bakuła Z, Marczak M, Bluszcz A, Proboszcz M, Kościuch J, Krenke R, Stakėnas P, Mokrousov I, Jagielski T. Phylogenetic relationships of Mycobacterium tuberculosis isolates in Poland: The emergence of Beijing genotype among multidrug-resistant cases. Front Cell Infect Microbiol. 2023, 13:1161905. doi: 10.3389/fcimb.2023.1161905.
2022
Lučiūnaitė A, Dalgėdienė I, Žilionis R, Mašalaitė K, Norkienė M, Šinkūnas A, Gedvilaitė A, Kučinskaitė-Kodzė I, Žvirblienė A. Activation of NLRP3 Inflammasome by Virus-Like Particles of Human Polyomaviruses in Macrophages. Front Immunol. 2022; 13:831815.
Sližienė A, Plečkaitytė M, Zaveckas M, Juškaitė K, Rudokas V, Žvirblis G, Žvirblienė A. (2022). Monoclonal antibodies against the newly identified allergen β-enolase from common carp (Cyprinus carpio). Food and Agricultural Immunology, 33, 129-149
Plikusiene I, Maciulis V, Juciute S, Ramanavicius A, Balevicius Z, Slibinskas R, Kucinskaite-Kodze I, Simanavicius M, Balevicius S, Ramanaviciene A. 2022. Investigation of SARS-CoV-2 nucleocapsid protein interaction with a specific antibody by combined spectroscopic ellipsometry and quartz crystal microbalance with dissipation. Journal of Colloid and Interface Science 626:113–122.
Drobysh M, Liustrovaite V, Baradoke A, Rucinskiene A, Ramanaviciene A, Ratautaite V, Viter R, Chen C-F, Plikusiene I, Samukaite-Bubniene U, Slibinskas R, Ciplys E, Simanavicius M, Zvirbliene A, Kucinskaite-Kodze I, Ramanavicius A. 2022. Electrochemical Determination of Interaction between SARS-CoV-2 Spike Protein and Specific Antibodies. International Journal of Molecular Sciences 23: 6768.
Grincevičienė Š, Vaitkienė D, Kanopienė D, Vansevičiūtė R, Tykvart J, Sukovas A, Celiešiūtė J, Ivanauskaitė Didžiokienė E, Čižauskas A, Laurinavičienė A, Král V, Hlavačková A, Zemanová J, Stravinskienė D, Sližienė A, Petrošiūtė A, Petrauskas V, Balsytė R, Grincevičius J, Navratil V, Jahn U, Konvalinka J, Žvirblienė A, Matulis D, Matulienė J. Factors, associated with elevated concentration of soluble carbonic anhydrase IX in plasma of women with cervical dysplasia. Sci Rep. 2022;12(1): 15397.
Matulienė J, Žvinys G, Petrauskas V, Kvietkauskaitė A, Zakšauskas A, Shubin K, Zubrienė A, Baranauskienė L, Kačenauskaitė L, Kopanchuk S, Veiksina S, Paketurytė-Latvė V, Smirnovienė J, Juozapaitienė V, Mickevičiūtė A, Michailovienė V, Jachno J, Stravinskienė D, Sližienė A, Petrošiūtė A, Becker HM, Kazokaitė-Adomaitienė J, Yaromina A, Čapkauskaitė E, Rinken A, Dudutienė V, Dubois LJ, Matulis D. Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells. Sci Rep. 2022;12(1): 17644.
Ruta Inciuraite, Rima Ramonaite, Juozas Kupcinskas, Indre Dalgediene, Ugne Kulokiene, Vytautas Kiudelis, Greta Varkalaite, Aurelija Zvirbliene, Laimas Virginijus Jonaitis, Gediminas Kiudelis, Andre Franke, Simonas Juzenas, Jurgita Skieceviciene. Crypt-top and crypt-bottom colonic epithelial cell microRNA profiling reveals cell type-specific response in active and quiescent ulcerative colitis. bioRxiv doi: 10.1101/2022.09.25.22280336
Widerspick L, Vázquez CA, Niemetz L, Heung M, Olal C, Bencsik A, Henkel C, Pfister A, Brunetti JE, Kucinskaite-Kodze I, Lawrence P, Muñoz Fontela C, Diederich S, Escudero-Pérez B. Inactivation Methods for Experimental Nipah Virus Infection. Viruses. 2022;14(5): 1052.
Inga Peciuliene, Egle Jakubauskiene, Laurynas Vilys, Ruta Zinkeviciute, Kotryna Kvedaraviciute, Arvydas Kanopka. Short-term hypoxia in cells induces expression of genes which are enhanced in stressed cells. Genes, 2022, 13, 1596.
KLIMASAUSKAS Saulius, RAKAUSKAITE Rasa, URBANAVICIUTE Giedrė, LASICKIENE Rita, SIMANAVICIUS Martynas, ZVIRBLIENE Aurelija. Antibodies for Photoactive Protein Manipulation. EP21187460.7
Monoclonal antibodies against common carp beta-enolase. Gintautas Zvirblis, Aiste Sliziene, Milda Pleckaityte, Mindaugas Zaveckas. EP4056595A1, 2022-09-14
Monokloniniai antikūnai prieš paprastojo karpio beta enolazę. Gintautas Žvirblis, Aistė Sližienė, Milda Plečkaitytė, Mindaugas Zaveckas. LT 69 62 B, 2022-12-12
2021
Jakubauskienė E, Kanopka A. 2021. Alternative Splicing and Hypoxia Puzzle in Alzheimer’s and Parkinson’s Diseases. Genes 12:1272. DOI: 10.3390/genes12081272.
Kučinskaitė-Kodzė, I., Simanavičius, M., Šimaitis, A., Žvirblienė, A. Persistence of SARS-CoV-2-Specific Antibodies for 13 Months after Infection. Viruses. 2021, 13(11): 2313
McNabb L, Andiani A, Bulavaite A, Zvirbliene A, Sasnauskas K, Lunt R. 2021. Development and validation of an IgM antibody capture ELISA for early detection of Hendra virus. Journal of Virological Methods 298:114296. DOI: 10.1016/j.jviromet.2021.114296.
Yu JC, Mietzsch M, Singh A, Jimenez Ybargollin A, Kailasan S, Chipman P, Bhattacharya N, Fakhiri J, Grimm D, Kapoor A, Kučinskaitė-Kodzė I, Žvirblienė A, Söderlund-Venermo M, McKenna R, Agbandje-McKenna M. 2021. Characterization of the GBoV1 Capsid and Its Antibody Interactions. Viruses 13:330. DOI: 10.3390/v13020330.
Plikusiene I, Maciulis V, Ramanaviciene A, Balevicius Z, Buzavaite-Verteliene E, Ciplys E, Slibinskas R, Simanavicius M, Zvirbliene A, Ramanavicius A. 2021. Evaluation of kinetics and thermodynamics of interaction between immobilized SARS-CoV-2 nucleoprotein and specific antibodies by total internal reflection ellipsometry. Journal of Colloid and Interface Science 594:195–203. DOI: 10.1016/j.jcis.2021.02.100.
Sarantopoulos, A., Brown, D.,Wiedermann, U., Alvarez, C.,Bogdan, C., Gürsel, I., Janković, I., LeClerc,C., Locati, M., Spurkland, A., Regateiro, F., Van Damme, P., Žvirblienė,A., Wensveen, F,M. The EFIS vaccination task force expert report. Eur. J. Immunol. 2021. 51: 1023–1027
2020
Grigas J, Simkute E, Simanavicius M, Pautienius A, Streimikyte–Mockeliune Z, Razukevicius D, Stankevicius A. Hepatitis E genotype 3 virus isolate from wild boar is capable of replication in non–human primate and swine kidney cells and mouse neuroblastoma cells. BMC Vet Res. 2020; 16:95
Rakauskaitė Rasa; Urbanavičiūtė Giedrė; Simanavičius Martynas; Lasickienė Rita; Vaitiekaitė Aušra; Petraitytė Gražina; Masevičius Viktoras; Žvirblienė Aurelija; Klimašauskas Saulius. Photocage-Selective Capture and Light-Controlled Release of Target Proteins. iScience. 2020; 23(12):101833
Lazutka J, Simutis K, Matulis P, Petraitytė-Burneikienė R, Kučinskaitė-Kodzė I, Simanavičius M, Tamošiūnas PL. Antigenicity study of the yeast-generated human parvovirus 4 (PARV4) virus-like particles. Virus Res. 2020; 198236
Kucinskaite–Kodze I, Simanavicius M, Dapkunas J, Pleckaityte M, Zvirbliene A. Mapping of recognition sites of monoclonal antibodies responsible for the inhibition of pneumolysin functional activity. Biomolecules. 2020; 10, 1009
Lučiūnaitė A, McManus RM, Jankunec M, Rácz I, Dansokho C, Dalgėdienė I, Schwartz S, Brosseron F, Heneka MT. Soluble Aβ oligomers and protofibrils induce NLRP3 inflammasome activation in microglia. J Neurochem. 2019 Dec 23:e14945
Mickiene, G., Dalgėdienė, I., Zvirblis, G., Dapkunas, Z., Plikusiene, I., Buzavaite-Verteliene, E., Balevičius, Z., Rukšėnaitė, A., & Pleckaityte, M. (2020). Human granulocyte-colony stimulating factor (G-CSF)/stem cell factor (SCF) fusion proteins: design, characterization and activity. PeerJ, 8, e9788
Bulavaitė A, Dalgediene I, Michailoviene V, Pleckaityte M. Type II Restriction-Modification System from Gardnerella vaginalis ATCC 14018. Pathogens. 2020;9(9):703
Špakova A, Dalgėdienė I, Insodaitė R, Sasnauskienė A, Žvirblienė A, Petraitytė-Burneikienė R. vB_EcoS_NBD2 bacteriophage-originated polytubes as a carrier for the presentation of foreign sequences. Virus Res. 2020 Dec;290:198194
Stravinskiene D, Sliziene A, Baranauskiene L, Petrikaite V, Zvirbliene A. Inhibitory Monoclonal Antibodies and Their Recombinant Derivatives Targeting Surface-Exposed Carbonic Anhydrase XII on Cancer Cells. International Journal of Molecular Sciences. 2020; 21(24):9411
Esser, C., Boots, A.M., Caignard, A., Ciraci, C., Grčević, D., Knapp, S., Montoya, M., Rosa, F.D., Saksida, T., Stravinskiene, D., et al. (2020). The impact of COVID-19 lock-downs for European (female) immunologists – our views as members of the EFIS gender and diversity task force. European Journal of Immunology 50, 1855–1857
2019
Stravinskiene D, Imbrasaite A, Petrikaite V, Matulis D, Matuliene J, Zvirbliene A. New Monoclonal Antibodies for a Selective Detection of Membrane-Associated and Soluble Forms of Carbonic Anhydrase IX in Human Cell Lines and Biological Samples. Biomolecules. 2019 pii: E304. doi: 10.3390/biom9080304
Takkinen K, Žvirblienė A. Recent advances in homogenous immunoassays based on resonance energy transfer. Curr Opin Biotechnol. 2019; 55: 16-22. doi: 10.1016/j.copbio.2018.07.003
Kols, N. I.; Aatola, H.; Peltola, V.; Xu, M.; Nora-Krukle, Z.; Hedman, K.; Zvirbliene, A.; Toivola, H.; Vuorinen, T.; Koskinen, J. M.; et al. Comparison of Phenotypic and Genotypic Diagnosis of Acute Human Bocavirus 1 Infection in Children. J. Clin. Virol. 2019, 120, 17–19.
Stravinskiene, D.; Imbrasaite, A.; Petrikaite, V.; Matulis, D.; Matuliene, J.; Zvirbliene, A. New Monoclonal Antibodies for a Selective Detection of Membrane-Associated and Soluble Forms of Carbonic Anhydrase IX in Human Cell Lines and Biological Samples. Biomolecules 2019, 9 (8), 304.
Ragaliauskas, T.; Plečkaitytė, M.; Jankunec, M.; Labanauskas, L.; Baranauskiene, L.; Valincius, G. Inerolysin and Vaginolysin, the Cytolysins Implicated in Vaginal Dysbiosis, Differently Impair Molecular Integrity of Phospholipid Membranes. Sci. Rep. 2019, 9 (1), 10606.
Peciuliene, I.; Vilys, L.; Jakubauskiene, E.; Zaliauskiene, L.; Kanopka, A. Hypoxia Alters Splicing of the Cancer Associated Fas Gene. Exp. Cell Res. 2019, 380 (1), 29–35.
Asta Lučiūnaitė, Róisín M. McManus, Marija Jankunec, Ildikó Rácz, Cira Dansokho, Indrė Dalgėdienė, Stephanie Schwartz, Frederic Brosseron, Michael T. Heneka. Soluble Aβ Oligomers and Protofibrils Induce NLRP3 Inflammasome Activation in Microglia. J Neurochem. 2019 Dec 23:e14945.
Book chapters
Stravinskienė, D.; Žvirblienė, A. Development of Therapeutic Antibodies Against Carbonic Anhydrases. In Carbonic Anhydrase as Drug Target; Matulis, D., Ed.; Springer International Publishing: Cham, 2019, pp 305–322.
Imbrasaitė, A.; Stravinskienė, D.; Žvirblienė, A. Detection of Carbonic Anhydrases. In Carbonic Anhydrase as Drug Target; Matulis, D., Ed.; 2019, pp 323–333.