Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics

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Science Translational Medicine
15 May 2013 vol 5, issue 185
http://stm.sciencemag.org/content/current

Vaccines
Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics
Philip R. Dormitzer, Pirada Suphaphiphat, Daniel G. Gibson, David E. Wentworth, Timothy B. Stockwell, Mikkel A. Algire, Nina Alperovich, Mario Barro, David M. Brown, Stewart Craig,     Brian M. Dattilo, Evgeniya A. Denisova, Ivna De Souza, Markus Eickmann, Vivien G. Dugan,     Annette Ferrari, Raul C. Gomila, Liqun Han, Casey Judge, Sarthak Mane, Mikhail Matrosovich,     Chuck Merryman, Giuseppe Palladino, Gene A. Palmer, Terika Spencer, Thomas Strecker,     Heidi Trusheim, Jennifer Uhlendorff, Yingxia Wen, Anthony C. Yee, Jayshree Zaveri, Bin Zhou,     Stephan Becker, Armen Donabedian, Peter W. Mason, John I. Glass, Rino Rappuoli, and J. Craig Venter
15 May 2013: 185ra68

Abstract
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.

http://stm.sciencemag.org/content/5/185/185ra68.abstract