Biochemistry (Moscow)

, Volume 77, Issue 1, pp 33–40 | Cite as

Plant-produced recombinant influenza vaccine based on virus-like HBc particles carrying an extracellular domain of M2 protein

  • N. V. RavinEmail author
  • R. Y. Kotlyarov
  • E. S. Mardanova
  • V. V. Kuprianov
  • A. I. Migunov
  • L. A. Stepanova
  • L. M. Tsybalova
  • O. I. Kiselev
  • K. G. Skryabin


Conventional influenza vaccines are based on a virus obtained in chicken embryos or its components. The high variability of the surface proteins of influenza virus, hemagglutinin and neuraminidase, requires strain-specific vaccines matching the antigenic specificity of newly emerging virus strains to be developed. A recombinant vaccine based on a highly conservative influenza virus protein M2 fused to a nanosized carrier particle can be an attractive alternative to traditional vaccines. We have constructed a recombinant viral vector based on potato X virus that provides for expression in the Nicotiana benthamiana plants of a hybrid protein M2eHBc consisting of an extracellular domain of influenza virus M2 protein (M2e) fused to hepatitis B core antigen (HBc). This vector was introduced into plant cells by infiltrating leaves with agrobacteria carrying the viral vector. The hybrid protein M2eHBc was synthesized in the infected N. benthamiana plants in an amount reaching 1–2% of the total soluble protein and formed virus-like particles with the M2e peptide presented on the surface. Methods of isolation and purification of M2eHBc particles from plant producers were elaborated. Experiments on mice have shown a high immunogenicity of the plant-produced M2eHBc particles and their protective effect against lethal influenza challenge. The developed transient expression system can be used for production of M2e-based candidate influenza vaccine in plants.

Key words

influenza vaccine plant biofactories M2 protein HBc antigen viral vector virus-like particle 



green fluorescent protein


hepatitis B virus nuclear antigen


the dose corresponding to 50% lethality


M2 protein extracellular domain of the influenza virus


phosphate-buffered saline


potato X virus

35S promoter

35S RNA promoter of the cauliflower mosaic virus

35S terminator

35S RNA terminator of the cauliflower mosaic virus


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Copyright information

© Pleiades Publishing, Ltd. 2012

Authors and Affiliations

  • N. V. Ravin
    • 1
    Email author
  • R. Y. Kotlyarov
    • 1
  • E. S. Mardanova
    • 1
  • V. V. Kuprianov
    • 1
  • A. I. Migunov
    • 2
  • L. A. Stepanova
    • 2
  • L. M. Tsybalova
    • 2
  • O. I. Kiselev
    • 2
  • K. G. Skryabin
    • 1
  1. 1.Centre “Bioengineering”Russian Academy of SciencesMoscowRussia
  2. 2.Research Institute of InfluenzaRussian Federation Ministry of Health and Social DevelopmentSt. PetersburgRussia

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