PANFLUVAC: Efficacious Vaccine Formulation System for Prophylactic Control of Influenza Pandemics
Title of Contribution:
PANFLUVAC: Efficacious Vaccine Formulation System for Prophylactic Control of Influenza Pandemics.
Author(s):
Kenneth C. McCullough1, Lisa J. Harwood1, Ronald Kompier2, Marieke Willemsen2, John Wood3, James S. Robertson3, Diane Major3,, John S. Oxford4, Alex Mann4, Rob Lambkin-Williams4, Stephanie Blanc4, Lars Haaheim5, Rebecca Cox5, Abdullah Madhun5, Maria Zambon6, Katja Hoschler6, Laura Campitelli7, Isabella Donatelli7, Carlos A. Guzman8, Thomas Ebensen8, Véronique Gobry9
Affiliation(s):
1Institute of Virology & Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland; 2Crucell N.V., 2301 CA Leiden, The Netherlands; 3National Institute for Biological Standards and Control, Potters Bar, South Mimms, Herts EN6 3QG, UK; 4Retroscreen Virology Ltd, Queen Mary’s School of Medicine and Dentistry, London E1 4NS, UK; 5Influenza Centre, University of Bergen, Department of Microbiology and Immunology, N-5021 Bergen, Norway; 6Respiratory Unit, HPA Colindale, London NW9 5HT, UK; 7National Influenza Centre, Istituto Superiore di Sanità, 00161 Rome, Italy; 8Helmholtz-Zentrum für Infektionsforschung, D-38124 Braunschweig,Germany; 9SCIPROM Sàrl, CH-1025 St-Sulpice, Switzerland.
Abstract:
The PANFLUVAC consortium has created a potentially efficacious vaccine against H5N1 virus, based on the NIBRG-14 reverse genetics engineered variant carrying the surface glycoproteins of A/Vietnam/1194/2004 (H5N1). Thereby, the aim is to provide vaccines promoting strong protection in a pandemic situation. These new H5N1 vaccines are based on virosome technology, with their vaccine potency enhanced using third generation ISCOM. Preclinical evaluation in mice, ferrets, pigs, rats and rabbits has shown the vaccine formulated in ISCOM to have high potential and efficacy. Consequently, a Phase I Clinical Trial of the first H5N1 virosomal vaccine will be pursued. In addition to this technology, the application of nanoparticle-based technology is providing a generic system for constructing efficacious vaccine delivery systems for the vaccines. The nanoparticles are modified to enhance vaccine potency by applying novel adjuvants targeting dendritic cells; these adjuvants also have high potential for classical formulation with influenza vaccines, at least. From this work, it has also been possible to generate a new in vitro system for fast-track testing of new vaccine delivery and adjuvant potential via high-throughput screening assays based on dendritic cells. The final element of this work will be to pursue the characterizations to determine whether heterotypic cross protection is offered by the new vaccines.
Overall, the results to date have resulted in the following: generation of the first virosomal H5N1 vaccine; identification of the parenteral route as more efficacious than nasal route (for this reason, the parenteral vaccinations are proceeding into clinical trials); identification of immunological correlates for mice, ferrets and pigs; identification of new generation adjuvants for nasal and parenteral application; identification of novel particulate vaccine delivery systems with dose sparing potential.
Acknowledgements
The PANFLUVAC Consortium gratefully acknowledges the help and advice of the European Commission (Project 044115), and all members of staff at Partner institutes who contributed to the work presented
