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Molecular Biology

, Volume 52, Issue 2, pp 269–271 | Cite as

Rabies Virus Glycoprotein with a Consensus Amino Acid Sequence and a Lysosome Targeting Signal Causes Effective Production of Antibodies in DNA-Immunized Mice

  • E. S. Starodubova
  • Y. V. Kuzmenko
  • E. O. Pankova
  • A. A. Latanova
  • O. V. Preobrazhenskaya
  • V. L. Karpov
Molecular Cell Biology

Abstract

Safe and effective anti-rabies vaccines are intensely sought worldwide. DNA vaccines have already shown their efficacy and safety and have occupied a special place in the field. Two prototype anti-rabies DNA vaccines were compared for the potential to induce virus-specific antibody production. One vector contained a codon-optimized gene with a territory-adapted consensus sequence of the rabies virus glycoprotein. The other one expressed the same glycoprotein in fusion with a c-CD63 lysosome targeting motif at the C terminus. ELISA of serum samples from immunized mice showed that the c-CD63 variant induced more efficient antibody production and shifted the IgG2a/IgG1 ratio towards the Th2-type immune response. The results gave grounds to believe that the approach successfully applied to the rabies glycoprotein may help to develop new-generation anti-rabies vaccines.

Keywords

rabies virus glycoprotein DNA vaccine CD63 lysosome 

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References

  1. 1.
    Kaur M., Garg R., Singh S., et al. 2015. Rabies vaccines: Where do we stand, where are we heading? Expert Rev. Vaccines. 14, 369–381.Google Scholar
  2. 2.
    Yang D.K., Kim H.H., Lee K.W., et al. 2013. The present and future of rabies vaccine in animals. Clin. Exp. Vaccine Res. 2, 19–25.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Tuchkov I.V., Nikiforov A.K. 2010. DNA immunization against rabies. Probl. Osobo Opasnykh Infekts. 104, 74–78.Google Scholar
  4. 4.
    Ferraro B., Morrow M.P., Hutnick N.A., et al. 2011. Clinical applications of DNA vaccines: Current progress. Clin. Infect. Dis. 53, 296–302.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Li L., Petrovsky N. 2016. Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev. Vaccines. 15, 313–329.CrossRefPubMedGoogle Scholar
  6. 6.
    Graham B.S. 2013. Advances in antiviral vaccine development. Immunol. Rev. 255, 230–242.CrossRefPubMedGoogle Scholar
  7. 7.
    Starodubova E.S., Kuzmenko Y.V., Latanova A.A., et al. 2016. Creation of DNA vaccine vector based on codon-optimized gene of rabies virus glycoprotein (G protein) with consensus amino acid sequence. Mol. Biol. (Moscow). 50 (2), 328–331.CrossRefGoogle Scholar
  8. 8.
    Starodubova E.S., Kuzmenko Y.V., Latanova A.A., et al. 2017. C-terminal lysosome targeting domain of CD63 modifies cellular localization of rabies virus glycoprotein. Mol. Biol. (Msocow). 51 (3), 404–407.CrossRefGoogle Scholar
  9. 9.
    Schroder J., Lullmann-Rauch R., Himmerkus N., et al. 2009. Deficiency of the tetraspanin CD63 associated with kidney pathology but normal lysosomal function. Mol. Cell. Biol. 29, 1083–1094.CrossRefPubMedGoogle Scholar
  10. 10.
    Ryu F., Takahashi T., Nakamura K., et al. 2000. Domain analysis of the tetraspanins: Studies of CD9/CD63 chimeric molecules on subcellular localization and upregulation activity for diphtheria toxin binding. Cell Struct. Funct. 25, 317–327.CrossRefPubMedGoogle Scholar
  11. 11.
    Feyssaguet M., Dacheux L., Audry L., et al. 2007. Multicenter comparative study of a new ELISA, PLATELIA RABIES II, for the detection and titration of antirabies glycoprotein antibodies and comparison with the rapid fluorescent focus inhibition test (RFFIT) on human samples from vaccinated and non-vaccinated people. Vaccine. 25, 2244–2251.CrossRefPubMedGoogle Scholar
  12. 12.
    Yang L.M., Zhao L.Z., Hu R.L., et al. 2006. A novel double-antigen sandwich enzyme-linked immunosorbent assay for measurement of antibodies against rabies virus. Clin. Vaccine Immunol. 13, 966–968.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cliquet F., McElhinney L.M., Servat A., et al. 2004. Development of a qualitative indirect ELISA for the measurement of rabies virus-specific antibodies from vaccinated dogs and cats. J. Virol. Methods. 117, 1–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Grabko V.I. 1991. RF Patent 2008355, December 18, 1991.Google Scholar
  15. 15.
    Kuzmenko Y.V., Tyutyaeva V.V., Andreev I.V., Sankov M.N., Starodubova E.S., Preobrazhenskaya O.V., Martynov A.I., Karpov V.L. 2013. Selection and immunological properties of allergen BetV2 drooping birch pollen with immunoregulatory signals. Immunologiya. 34, 213–217.Google Scholar
  16. 16.
    Mironov A.N., Bunatyan N.D., et al. 2012. Rukovodstvo po provedeniyu doklinicheskikh ispytanii lekarstvennykh sredstv (Guidelines for Conducting Preclinical Trials of Drugs). Moscow: Grif i K.Google Scholar
  17. 17.
    Kaur M., Rai A., Bhatnagar R. 2009. Rabies DNA vaccine: No impact of MHC class I and class II targeting sequences on immune response and protection against lethal challenge. Vaccine. 27, 2128–2137.CrossRefPubMedGoogle Scholar
  18. 18.
    Lu Y., Raviprakash K., Leao I.C., et al. 2003. Dengue 2 PreM-E/LAMP chimera targeted to the MHC class II compartment elicits long-lasting neutralizing antibodies. Vaccine. 21, 2178–2189.CrossRefPubMedGoogle Scholar
  19. 19.
    Anwar A., Chandrasekaran A., Ng M.L., Marques E., August J.T. 2005. West Nile premembrane-envelope genetic vaccine encoded as a chimera containing the transmembrane and cytoplasmic domains of a lysosome-associated membrane protein: Increased cellular concentration of the transgene product, targeting to the MHC II compartment, and enhanced neutralizing antibody response. Virology. 332, 66–77.CrossRefPubMedGoogle Scholar
  20. 20.
    Rigato P.O., Maciel M., Jr., Goldoni A.L., et al. 2012. Maternal LAMP/p55gagHIV-1 DNA immunization induces in utero priming and a long-lasting immune response in vaccinated neonates. PLoS One. 7, e31608.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • E. S. Starodubova
    • 1
  • Y. V. Kuzmenko
    • 1
  • E. O. Pankova
    • 1
  • A. A. Latanova
    • 1
  • O. V. Preobrazhenskaya
    • 1
  • V. L. Karpov
    • 1
  1. 1.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia

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