Novel Antigen-Adjuvant Vechicle as an Effective Influenza Vaccine
One of the biggest challenges concerning influenza vaccination is trying to keep up with the virus's mutational variation. The currently approved vaccines work by stimulating the body's immunity against the haemagglutinin and neuraminidase proteins on the virus's surface. As these proteins are prone to mutation, vaccines only induce immunity against specific subtypes of the virus. However, the influenza virus has a third protein in its outer coat, M2, and the extracellular domain of this protein, M2e, has been remarkably conserved in the amino acid sequence since human influenza virus was first isolated in 1933. If this protein could stimulate an adequate immune response it might be possible to develop a broad-spectrum vaccine against all influenza A subtypes.
Previous research has shown that when the extracellular domain of M2 (M2e) is linked to appropriate carrier particles, such as the hepatitis B virus core, it becomes highly immunogenic, inducing antibodies that fully protect mice against a potentially lethal influenza infection. Swedish biotech company Biovitrum AB has teamed up with researchers at the Flanders Interuniversity Institute for Biotechnology in Ghent (BE), who initially worked on the M2 protein, European SMEs Pepscan (the Netherlands), Proxima (UK) and Gteborg University to develop what could become the first universal vaccine for influenza. It could provide lifelong immunity against the virus and thus provide far greater protection in the event of a pandemic. It may even help to eradicate the disease in humans.
The unique combination of the consortium for the rational design of a mucosal influenza vaccine is unprecedented in European vaccine research. If the universal vaccine proves successful in clinical trials it will not only help to diminish the social and economic costs of influenza, but also secure the growth and development of the European vaccine industry in the global market.[+] Read More
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. Current influenza vaccines are based on the major influenza glycoproteins haemagglutinin (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. Furthermore, 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 aim of the Universal Vaccine project is to develop a powerful, new, safe and easily-administered nasal vaccine for humans that provides lifelong protection against influenza.
The scientific excellence and technologies within the consortium will be combined to design, develop, formulate and evaluate novel M2e-based 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. In the longer perspective the project may help reduce or even eradicate influenza infections in humans.
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 in 1933, despite numerous epidemics and at least two major pandemics. Therefore, by utilising 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:
For reasons of safety, efficacy and cost, mucosal administration of vaccines is today a priority for immunising 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 long term effect of a conceptually novel influenza vaccine will contribute to reducing and perhaps even eradicating influenza infections in humans.
TThe Universal Vaccine project will play a pivotal role in 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 commercialisation.