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Laboratory of Influenza Vaccines

Laboratory Lead — Lyudmila M. Cybalova, Dr.Med.Sci.

Phone: +7 (812) 234–62–61

E-mail: sovet@influenza.spb.ru









The Laboratory of Influenza Vaccines was formed in 2007 and is engaged in development and trials of safe, immunogenic and effective antiviral vaccines.

Primary Activities:

  • Creation of recombinant influenza vaccine based on conservative viral proteins. Currently, multiple variants of recombinant influenza vaccine containing M2 outer domain with different carriers(HBcAg, CPMV, Tobacco mosaic virus (TMV)) are under investigation. Hybrid proteins were obtained by Biology Faculty staff of Moscow State University (Faculty Lead — A. Atabekov, RAS member)
  • Biological, molecular and genetic characterization of a novel influenza A strain, which is a universal internal gene donor of for vaccine strains
The laboratory is one of the main contractors of the State Research Program «Influenza Vaccines with Wide Action Spectrum: Development, Production, Trials» (2014). Additionally, the lab is involved in a number of projects:

  • Development of Recombinant Influenza Vaccine Based on Highly Conservative Viral Proteins (2010–2012). State Contract №02.740.11.08772
  • «Protein Production in Plants», in the framework of №227056 «Plant-Produced Vaccines» European Project (in collaboration with the Federal Science and Innovations Agency and RAS Bioengineering Centre)
  • Equine Influenza: Epizootic Surveillance and Development of Means of Specific Diagnosis and Prevention (2010–2012). Joint international project with the Republic of Kazakhstan

Notable Achievements:

  • Several variants of recombinant influenza proteins containing avian influenza M2 outer domain were tested on laboratory animals, their toxicity immunogenicity and protective efficacy evaluated. The studies showed efficacy and feasibility of further developments
  • Biological, molecular and genetic characterization of a universal internal gene donor for vaccine strains was carried out. The donor shows high reproduction rate, equal to that of the current donor A/PR/8/34, and full human attenuation, which allows for using the new donor in live and inactivated vaccine production
  • Based on A/Hong Kong/1/68/162/35 (H3N2) universal donor, á/H5N1, A/H3N8, A/H3N2 and A/H1N1 reassortants were acquired. It was proven that reassortants received useful traits from their donor — high reproductive rates and attenuation sign
  • The lab developed A/Perth/16/09 (H3N2) master strain, which shows high reproductive rate, safety and genetic stability
  • Antigenic reassortants for typing HA and NA of modern and obsolete human influenza A strains, starting from 1946, were acquired
  • The lab conducted experimental study of efficacy of photodynamic virus inactivation system «Theraflex — MB Plasma» (France) in fresh–frozen donor blood plasma using several DNA and RNA virus models
  • In the framework of a joint project with Kazakhstan National Biotechnology Centre, experimental specimen of inactivated whole A/H5N1 vaccine were produced and necessary regulatory documents (Production Guidelines, Guidelines for the Use) developed

Research Techniques:

Vaccine strains are produced through reassortation and reverse genetics. Morphological studies of biopreparations are conducted with the help of electron microscopy. The lab utilizes a multitude of assays(IFA, HIA, Microneutralization Assay, Western–Immunoblotting, Flow Cytofluorometry, etc) to explore immunogenic properties of preparations. Immune response studies after immunizing laboratory animals with vaccines of variable dose, immunization scheme and route of administration, involve IgM, IgA, IgG Isotype serum antibodies for specific immune response, secretory IgA for local immune response, T–lymphocytes phenotyping, cell activation markers, central and effector memory cells type Tx1 and Tx2, intercellular cytokine production for cellular immune response.

Cell cultures, chicken embryos and laboratory animals are used for investigating protective efficacy of various preparations. The lab also works with human and avian influenza viruses, parainfluenza viruses, adenoviruses and other viral infections. For human hepatitis B, C and Coronavirus, animal model viruses are used: Duck hepatitis B virus, Bovine Diarrhea Virus and Avian infectious bronchitis virus, respectively.

Equipment:

  • BD FACSCanto II Flow Cytometer
  • CO2 Incubator, transilluminator
  • Bio Rad Plate Spectrophotometer
  • Horizontal and vertical electrophoresis chambers
  • MSC.12 Laminar box
  • SF56 Spectrophotometer
  • AV 120-01C Analytical weights
  • Biolam P2-1 biological inverted-stage microscope
  • Ultraviolet Air Treatment systems, electrostatic air purifier, water ultrafiltration system, thermostats, centrifuges, refrigerating chambers

Interinstitutional and International Relations:

  • RAS Bioengineering Centre
  • Lomonosov Moscow State University
  • RAMS Institute of Experimental Medicine (IEM)
  • National Technology Institute of Poultry Farming
  • Avir Green Hills Biotechnology Research Development Trade AG, Vienna, Austria
  • Jonn Innes Centre, Norwich, UK
  • National Centre for Biotechnology of the Republic of Kazakhstan

Selected Publications:

  • O.K. Kuznetsov. Use of Influenza Vaccines before and during Pandemic. Epidemiology and Vaccinal Prevention. 2007(1):31–37, 2007(2):39–43 In Russian
  • O.I. Kiselev, L.M.Tsybalova. The Current state of H5N1 vaccine development in Russia and Worldwide. Avian Influenza. The Origin of Infectious Disasters. 2007. p175-181. In Russian
  • L.M. Tsybalova, O.I. Kiselev. Problems and Perspectives of Vaccinal Prophylaxis during Pandemic. Epidemiology and Vaccinal Prevention. 2007;46(3):39–47
  • L.M.Tsybalova, E.V. Timofeeva, Buzitskaya, J.V., Gudkova, T.M., Maksakova, V.L., Parkov, O.V. Epidemic Process of Rubella during Mass Vaccination of Children. Zh Mikrobiol Epidemiol Immunobiol. 2009;(5):47–51
  • Yu. A. Meshcheryakova, M. A. Eldarov, A. I. Migunov, L. A. Stepanova and I. A. Repko, et al. Cowpea Mosaic Virus Chimeric Particles Bearing the Ectodomain of Matrix Protein 2 (M2E) Of the Influenza a Virus: Production and Characterization. Mol Biol. 2009;43(4):741–50. In Russian
  • D.B. Golubev, O.K. Kuznetsov. The Expectation of Influenza Pandemic. Epidemiology and Vaccinal Prevention. 2009(3):5–11. In Russian
  • R.Y. Kotlyarov, V.V. Kuprianov, A.I. Migunov, L.A. Stepanova, L.M. Tsybalova, O.I. Kiselev, N.V. Ravin, K.G. Skryabin. Development Of Recombinant Vaccine Against A(H1N1) 2009 Influenza Based On Virus-Like Nanoparticles Carrying The Extracellular Domain Of M2 Protein. Acta Naturae. 2010;2(5):75–80
  • O.K. Kuznetsov, L.A. Stepanova, E.G. Golovacheva, O.V. Gashinskay. Duration of Actively Obtained Immune Response from Influenza. Med. AÓad. Journ. 2010;2(1):15–26 In Russian
  • L.M. Tsybalova, L.S. Karpova, A.B. Komissarov, M.Yu. Eropkin, M.P. Grudinin, O.I. Kiselev. Influenza A(H1N1) 2009 Pandemic In Russia. News of the Russian Academy of Medical Sciences. 2011 №2