017749
COOP-CT-2005
Universal Vaccine
The overall objective of the proposed project is to integrate the combined scientific excellence and technologies of the SME proposers and RTD performers to establish technology platforms, produce novel prototype candidate influenza vaccines and evaluate vaccine efficacy and safety in preclinical models.
Biovitrum AB, Sweden
Pepscan Systems BV, The Netherlands
Proxima Concepts Ltd, England
Eurogentec SA, Belgium
Flanders Interuniversity Institute for Biotechnology VZW (VIB), Belgium
Göteborg University (UGOT), Sweden
€ 1 722 574
€ 1 154 717
Biovitrum AB
Arvid Wallgrens Backe 20
SE-413 46 Göteborg,
Sweden
www.biovitrum.com
Anna Ramne, PhD, Project Manager, Biovitrum AB
E-mail: anna.ramne@biovitrum.com
The aim of the Universal Vaccine project is to develop a powerful, new, safe and easily-administered nasal vaccine for humans that provides a life-long protection against influenza. In the longer perspective the project may help reduce or even eradicate influenza infections in humans.
Influenza is a recurrent global threat and affects millions of people in the world every year. Vaccination constitutes undoubtedly the most cost-effective preventive measure against morbidity and death from infectious diseases such as influenza. Most vaccines today are injectable and use aluminium salts as their adjuvant component. However, there is general agreement that needle-free vaccines are preferable for reasons of improved patient comfort and ease of administration, as well as reducing the risk of contamination and other adverse effects, while promoting compliance and increasing the safety of vaccination. Moreover, for respiratory diseases like influenza, nasal delivery brings the vaccine to where it is most needed to stimulate a local immune response, namely the respiratory tract.
The Universal Vaccine project strives to meet this medical need by employing a highly innovative strategy that represents a conceptually novel way of rationally designing a vaccine against influenza. The scientific excellence and technologies within the consortium will be combined to design, develop, formulate and evaluate novel influenza vaccine candidates with the aim of achieving improved efficacy, longer lasting protection and broad-spectrum immunity against the diversity of influenza strains, exceeding the performance of current annual influenza vaccines.
Current influenza vaccines are based on the major influenza glycoproteins hemagglutinin (HA) and neuraminidase (NA) as antigenic determinants. However, these proteins are subject to mutation (drift) and gene re-assortment (shift) generating seasonal variations in the circulating influenza strains thereby rendering this type of vaccine less efficient in long term protection against viral infection and necessitating annual updates of the vaccine components. The development of a universal influenza vaccine is based on the identification of an extracellular domain of the minor influenza protein M2 protein, referred to as M2e. The sequence of the M2e domain has been highly conserved since the first isolation of human influenza virus since 1933, despite numerous epidemics and at least two major pandemics. Therefore, by utilizing the M2e peptide as antigenic determinant a vaccine will be created that could provide long term protection against a broader spectrum of influenza strains.
The development of needle-free vaccines has been hampered by the lack of effective mucosal adjuvants. Cholera toxin (CT) and the closely related Escherichia coli heat-labile toxin (LT) are powerful mucosal adjuvants but have proved unsuitable in the clinical setting due to their inherent toxicity and potential association with Bell’s palsy (paralysis of the facial nerve). A novel mucosal adjuvant, CTA1-DD, has been developed which combines the enzymatic activity of the A1 unit of cholera toxin with a dimer of the Ig-binding element of Staphylococcus aureus Protein A, thereby targeting the adjuvant specifically to B-cells and other Ig-binding cells of the immune system. This strategy has proved successful in that the CTA1-DD adjuvant is completely non-toxic and, despite its more selective binding properties, has retained potent mucosal and systemic immunoenhancing functions making it a highly suitable adjuvant for development of new, efficient mucosal vaccines.
The operational goals of the project are to:
Covalently fuse the M2e-peptide with the CTA1-DD adjuvant, creating a strongly immunogenic influenza vaccine suitable for mucosal delivery
Further improve vaccine efficacy by incorporating the fusion protein in proprietary liposomes
Increase the in vivo maintenance of the antigen by using blocked or constrained peptides or peptidomimetics
Determine the in vivo mechanism of action of the mucosal influenza vaccine
Demonstrate the safety and efficacy of the vaccine in animal challenge models
For reasons of safety, efficacy and cost, mucosal administration of vaccines is today a priority for immunizing against mucosal as well as systemic infections. The ease of administration of needle-free vaccines facilitates their distribution to larger populations, particularly in the developing world, while improving vaccination safety and compliance. This will have great positive impact on global health and immense societal gains.
The development of a nasal universal influenza vaccine will greatly simplify and economise influenza vaccination. Patient benefits will include less discomfort by the non-invasive route of administration and reduced frequency of immunizations throughout life. The long term effect of a conceptually novel influenza vaccine will contribute to reduce and may even eradicate influenza infections in humans.
The Universal Vaccine project will play a pivotal role for the future development and competitiveness of the SMEs involved. A successful novel mucosal vaccine against influenza would have significant impact on the global market and secure growth and development of the European vaccine industry. The results of the project will be investigated for patentable knowledge and it is anticipated that the SMEs could establish themselves firmly on the market for mucosal vaccines. Their extended and potentially stronger IP would allow expansion of their respective business areas and open up new opportunities for exploitation and commercialization.
This project is funded by the European Commission’s Sixth Framework Scientific Programme Co-operative Research Projects. The European Community is not liable for any use that might be made of the information in this project presentation.