Nina V Tikunova

Publications (5)10.52 Total impact

• Article: Combinatorial antibody library from multiple sclerosis patients reveals antibodies that cross-react with myelin basic protein and EBV antigen.

  Alexander G Gabibov, Alexey A Belogurov, Yakov A Lomakin, Maria Yu Zakharova, Marat E Avakyan, Viktorya V Dubrovskaya, Ivan V Smirnov, Alexis S Ivanov, Andrey A Molnar, Vladimir E Gurtsevitch, Sergey V Diduk, Ksenia V Smirnova, Bérangère Avalle, Svetlana N Sharanova, Alfonso Tramontano, Alain Friboulet, Alexey N Boyko, Natalia A Ponomarenko, Nina V Tikunova
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  ABSTRACT: Multiple sclerosis (MS) is a widespread neurodegenerative autoimmune disease with unknown etiology. It is increasingly evident that, together with pathogenic T cells, autoreactive B cells are among the major players in MS development. The analysis of myelin neuroantigen-specific antibody repertoires and their possible cross-reactivity against environmental antigens, including viral proteins, could shed light on the mechanism of MS induction and progression. A phage display library of single-chain variable fragments (scFvs) was constructed from blood lymphocytes of patients with MS as a potential source of representative MS autoantibodies. Structural alignment of 13 clones selected toward myelin basic protein (MBP), one of the major myelin antigens, showed high homology within variable regions with cerebrospinal fluid MS-associated antibodies as well as with antibodies toward Epstein-Barr latent membrane protein 1 (LMP1). Three scFv clones showed pronounced specificity to MBP fragments 65-92 and 130-156, similar to the serum MS antibodies. One of these clones, designated E2, in both scFv and full-size human antibody constructs, was shown to react with both MBP and LMP1 proteins in vitro, suggesting natural cross-reactivity. Thus, antibodies induced against LMP1 during Epstein-Barr virus infection might act as inflammatory trigger by reacting with MBP, suggesting molecular mimicry in the mechanism of MS pathogenesis.
  The FASEB Journal 08/2011; 25(12):4211-21. · 5.71 Impact Factor
• Article: Chimeric antibodies against tick-borne encephalitis virus.

  Lev N Levanov, Leonid E Matveev, Elena P Goncharova, Leonid R Lebedev, Alexander B Ryzhikov, Tatyana E Yun, Tatyana A Batanova, Alexander N Shvalov, Ivan K Baykov, Lyudmila N Shingarova, Michael P Kirpichnikov, Nina V Tikunova
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  ABSTRACT: Two chimeric antibodies (ch) 13D6 and 10C2 against the glycoprotein E of tick-borne encephalitis virus (TBEV) were constructed by fusing variable regions of murine monoclonal antibodies (Mabs) 13D6 and 10C2 to human constant regions. Monovalent analogues of these antibodies in format of single-chain antibodies (scFv or sc) were developed, as well. The ch13D6, ch10C2, sc13D6 and sc10C2 exhibited binding characteristics similar to parental Mabs. Only the ch13D6 and sc13D6 were able to neutralize TBEV infectivity in vitro. The in vitro neutralization provided by ch13D6 suggests that this antibody can be further developed into a potent prophylaxis and therapy for tick-borne encephalitis (TBE) infection.
  Vaccine 07/2010; 28(32):5265-71. · 3.77 Impact Factor
• Article: Recombinant analogs of a novel milk pro-apoptotic peptide, lactaptin, and their effect on cultured human cells.

  Dmitry V Semenov, Alexander S Fomin, Elena V Kuligina, Olga A Koval, Vera A Matveeva, Irina N Babkina, Nina V Tikunova, Vladimir A Richter
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  ABSTRACT: We recently isolated and characterized a human milk peptide, lactaptin, which induced apoptosis of cultured human MCF-7 cells. Lactaptin was identified as a proteolytic fragment of human kappa-casein. Here, we generated two recombinant analogs of the peptide, RL1 and RL2, containing truncated and complete amino acid sequences of lactaptin, respectively. Analogs were produced in E.coli, purified and assayed for biological activity on cultured human MCF-7 cells. RL1 was shown to induce only a small decrease in cell viability, whereas RL2 lowered the viability of MCF-7 cells by 60%. This reduction in MCF-7 cell viability was associated with apoptosis, which was indicated by phosphatidilserine externalization and caspase-7 activation. The viability of A549 and Hep-2 cells was also reduced by RL2, albeit to a lesser degree than seen with MCF-7 cells; this reduced viability was not accompanied by apoptosis. Non-malignant human mesenchymal stem cells (MSC) were completely resistant to RL2 action.
  The Protein Journal 03/2010; 29(3):174-80. · 1.04 Impact Factor
• Article: Application of bioinformatics resources for genosensor design.

  Tamara M Khlebodarova, Nina V Tikunova, Alla V Kachko, Irina L Stepanenko, Nikolai L Podkolodny, Nikolai A Kolchanov
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  ABSTRACT: Two novel databases, GenSensor and ConSensor, have been developed. GenSensor accumulates information on the sensitivities of the prokaryotic genes to external stimuli and may facilitate designing of novel genosensors; ConSensor contains data about the structure and efficiency of the available genosensor plasmid constructs. Using these databases, candidate genes for the design of novel multiple functional genosensors were searched, and the Escherichia coli dps gene was chosen as the candidate. The genetic construct derived from its promoter was developed and tested for its sensitivity to various stress agents: hydrogen peroxide (oxidative stress), phenol (protein and membrane damaging), and mitomycin C (DNA damaging). This genosensor was found to be sensitive to all stress conditions applied confirming its ability to serve as multi-functional genosensor. The GenSensor and ConSensor databases are available at http://wwwmgs.bionet.nsc.ru/mgs/dbases/gensensor/index.html.
  Journal of Bioinformatics and Computational Biology 05/2007; 5(2B):507-20.
• Article: Application of Bioinformatics Resources for Genosensor Design.

  Tamara M. Khlebodarova, Nina V. Tikunova, Alla V. Kachko, Irina L. Stepanenko, Nikolay L. Podkolodny, Nikolay A. Kolchanov
  J. Bioinformatics and Computational Biology. 01/2007; 5:507-520.