Synthetic generation of influenza vaccine viruses for rapid response to pandemics

Sci Transl Med. 2013 May 15;5(185):185ra68. doi: 10.1126/scitranslmed.3006368.


During the 2009 H1N1 influenza pandemic, vaccines for the virus became available in large quantities only after human infections peaked. To accelerate vaccine availability for future pandemics, we developed a synthetic approach that very rapidly generated vaccine viruses from sequence data. Beginning with hemagglutinin (HA) and neuraminidase (NA) gene sequences, we combined an enzymatic, cell-free gene assembly technique with enzymatic error correction to allow rapid, accurate gene synthesis. We then used these synthetic HA and NA genes to transfect Madin-Darby canine kidney (MDCK) cells that were qualified for vaccine manufacture with viral RNA expression constructs encoding HA and NA and plasmid DNAs encoding viral backbone genes. Viruses for use in vaccines were rescued from these MDCK cells. We performed this rescue with improved vaccine virus backbones, increasing the yield of the essential vaccine antigen, HA. Generation of synthetic vaccine seeds, together with more efficient vaccine release assays, would accelerate responses to influenza pandemics through a system of instantaneous electronic data exchange followed by real-time, geographically dispersed vaccine production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Computer Simulation
  • Dogs
  • Genes, Synthetic
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Humans
  • Influenza A Virus, H7N9 Subtype / immunology
  • Influenza A virus / immunology*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Madin Darby Canine Kidney Cells
  • Neuraminidase / genetics
  • Pandemics / prevention & control*
  • Reassortant Viruses / immunology
  • Reproducibility of Results
  • Vaccines, Synthetic / immunology*
  • Viral Load


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Vaccines, Synthetic
  • Neuraminidase