VACCINO ANTINFLUENZALE

VACCINI: trOvato un piu' rapido metodo di produzione del vaccino antinfluenzale. sara' utile in caso di necessita' di fronte ad una eventuale paNDEMIA.

Synthetic Generation of Influenza Vaccine Viruses for 

Rapid Response to Pandemics

1. Philip R. Dormitzer¹,*, 
2. Pirada Suphaphiphat¹, 
3. Daniel G. Gibson²,³,⁴, 
4. David E. Wentworth²,
5. Timothy B. Stockwell², 
6. Mikkel A. Algire², 
7. Nina Alperovich², 
8. Mario Barro⁵, 
9. David M. Brown²,
10. Stewart Craig¹, 
11. Brian M. Dattilo⁵, 
12. Evgeniya A. Denisova², 
13. Ivna De Souza¹, 
14. Markus Eickmann⁶,
15. Vivien G. Dugan²,†, 
16. Annette Ferrari¹, 
17. Raul C. Gomila¹,⁷, 
18. Liqun Han¹, 
19. Casey Judge¹, 
20. Sarthak Mane¹,
21. Mikhail Matrosovich⁶, 
22. Chuck Merryman³, 
23. Giuseppe Palladino¹, 
24. Gene A. Palmer¹, 
25. Terika Spencer¹,⁸,
26. Thomas Strecker⁶, 
27. Heidi Trusheim⁸, 
28. Jennifer Uhlendorff⁶, 
29. Yingxia Wen¹, 
30. Anthony C. Yee²,
31. Jayshree Zaveri², 
32. Bin Zhou², 
33. Stephan Becker⁶, 
34. Armen Donabedian⁵, 
35. Peter W. Mason¹, 
36. John I. Glass²,
37. Rino Rappuoli¹,⁷ and 
38. J. Craig Venter²,³,⁴

1. ¹Novartis Vaccines and Diagnostics, Cambridge, MA 02139, USA.
2. ²The J. Craig Venter Institute, Rockville, MD 20850, USA.
3. ³The J. Craig Venter Institute, San Diego, CA 92121, USA.
4. ⁴Synthetic Genomics Inc., La Jolla, CA 92037, USA.
5. ⁵Biomedical Advanced Research and Development Authority, U.S. Department of Health and Human Services, Washington, DC 20201, USA.
6. ⁶Institut für Virologie, Philipps-Universität Marburg, D-35032 Marburg, Germany.
7. ⁷Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
8. ⁸Novartis Vaccines and Diagnostics, Holly Springs, NC 25740, USA.

• ↵† Present address: Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.

1. ↵*Corresponding author. E-mail: philip.dormitzer@novartis.com

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.

• Copyright © 2013, American Association for the Advancement of Science

Citation: P. R. Dormitzer, P. Suphaphiphat, D. G. Gibson, D. E. Wentworth, T. B. Stockwell, M. A. Algire, N. Alperovich, M. Barro, D. M. Brown, S. Craig, B. M. Dattilo, E. A. Denisova, I. D. Souza, M. Eickmann, V. G. Dugan, A. Ferrari, R. C. Gomila, L. Han, C. Judge, S. Mane, M. Matrosovich, C. Merryman, G. Palladino, G. A. Palmer, T. Spencer, T. Strecker, H. Trusheim, J. Uhlendorff, Y. Wen, A. C. Yee, J. Zaveri, B. Zhou, S. Becker, A. Donabedian, P. W. Mason, J. I. Glass, R. Rappuoli, J. C. Venter, Synthetic Generation of Influenza Vaccine Viruses for Rapid Response to Pandemics. Sci. Transl. Med. 5, 185ra68 (2013).