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Novel antigen-adjuvant vehicle as an effective influenza vaccine

Final Report Summary - UNIVERSAL VACCINE (Novel antigen-adjuvant vehicle as an effective influenza vaccine)

Current influenza vaccines have several draw backs. First, they are manufactured annually and based on the influenza viral strains that the WHO recommend approximately nine months prior to the next influenza season. Consequently, there is always a risk that the annual influenza vaccine is off target and does not provide a satisfactory protection against infection by the circulating influenza strains. Further, the annual vaccines are produced by a laborious method involving use of embryonated chicken eggs. This method is both time consuming and costly, making vaccine supplies limited and does not allow for rapid changes in manufacturing should novel influenza strains arise. Individuals that are allergic to egg products are also excluded from the possibility of utilising these vaccines. The majority of the annual influenza vaccines are administered via injection which encompasses major patient discomfort both by the invasive administration and the necessity for patients to have to visit their physician for the flu shot.

The goal of this project was to develop a novel influenza vaccine that addresses all these issues in that the final vaccine will have the following benefits over current influenza vaccines:
- provide broad protection against a wider variety of influenza strains;
- easy to administer via the intranasal route, which arm the patient with both a mucosal response at the line of enemy attack and also a systemic protection
- produced by a none-egg based method.

In this project, the initial steps for generating novel influenza vaccine candidates were to optimise the various components that would potentially be part of the vaccines. The second period focused on evaluating the vaccine candidates and examining key elements important for the vaccine efficacy.

Formulating the vaccine is imperative for the adequate delivery of the all components to mount a correct immune response. Proxima's proprietary vaccine delivery system (Vaxcine) is based on use of oils as carriers of the antigen and adjuvant to the cells of the immune system responsible for processing and presentation of antigenic materials. By adding oils to already immunogenic materials, the immune response can be further enhanced, thereby increasing the efficacy of the vaccine. Proxima has worked on formulating the different components of the vaccine and these have been tested both in vitro and in vivo. A variety of oils have been used to create reverse micelles and by designing the M2e antigen peptide with lipid tails conjugated ordinary micelles have also be formulated.

The work conducted supports the hypothesis that a universal influenza vaccine can be developed based on the rationale of this joint research and development collaboration. We have developed several vaccine candidates which provide protection in a mouse challenge model and demonstrate adequate and relevant immunologic responses and so far, no results have been obtained which indicate any major obstacle in the onwards development work. By refining the composition of the various vaccine parts, an optimal candidate vaccine product protected by novel IPR is likely to be developed within the framework of this programme. Concomitantly, important knowledge regarding immune mechanisms involved in host protection against viral infection will be generated. This may in addition have a general impact on future vaccine design.

The SME partners are using their respective regular channels and methods for exploitation and commercialisation of results to initiate contacts with potential industrial partners and customers in the pharmaceutical industry. The project coordinator (PCO) is appointed to act on behalf of the co-owners and will be responsible for negotiations with potential industrial partners who have expressed an interest in licensing the jointly owned knowledge. The PCO is also be responsible for negotiations regarding the terms for access right to any pre-existing know-how which is to be presented to a potential industrial partner.

The co-ownership agreement shall in detail define the rights and obligations of the PCO, or any other party appointed to act as coordinator on behalf of the co-owners as the case may be, in the course of negotiations and when entering into agreements with industrial partners.

This plan will act as a complement to the consortium agreement, which regulates IP issues in detail, i.e. the filing of patents and licensing issues. This promotes efficient and conflict-free interaction between the partners, while protecting the IP created in the project. CTA1-(M2e)x-DD represents two novel fusion proteins harbouring one or multiple copies of the M2e peptide incorporated between the CTA1 and DD domains. A hitherto unknown MHC class II restricted T cell epitope has been identified in the M2e peptide, which complements the potent B cell epitope present, and this combination may have significant beneficial effects on the efficacy of a universal anti-influenza A virus vaccine.

Within the framework of this programme partner 1 (BVT) and 6 (UGOT) have conceived, constructed, produced and characterised the novel proteins. Partner 2 (Pepscan) have synthesised M2e- peptide sequences. Partner 5 (VIB) has demonstrated in vivo that intranasal administration of these fusion proteins provides protection against a lethal challenge with a mouse adapted influenza strain.

These novel fusion proteins represent putative influenza vaccine candidates, comprising both the relevant influenza specific peptide and the functional mucosal adjuvant within the same molecule. With the knowledge of the beneficial effects of having a potent B cell epitope complemented with a T helper- and CTL-epitope and their role in protective immunity against influenza A virus it may be possible to develop even more potent mucosal influenza vaccines. As such they could be exploited as vaccine products either directly within the context of a potential spin out from the consortium or as a component in a sub-licensing deal with a major vaccine company.

The partners forming this consortium all agree to continue to promote dissemination of the results that have been acquired within the project. This work holds high priority in the consortium. The partners will, however, always consider the patentability and potential commercial exploitation of results prior to any publication. Dissemination will be achieved by means of publishing research results in international peer-review journals (e.g. European Journal of Immunology, Vaccine, Nature and Journal of Virology) using original material from the project, speaking at international scientific conferences, and filing patents. The consortium will also have an official presentation through the intra-project website where the results of the project can be presented to the public.

A website specific for the UNIVERSAL VACCINE project was set up with the address: http://www.universalvaccine.org. This site has two parts, one external domain with general information on the project such as a project summary, project presentation, a list of the consortium participants with links to their home pages, publications, press releases and public statements. The internal website can only be accessed by members of the consortium and is used as a document repository and for internal communication. All data results are deposited there as well as internal reports, power point presentations and minutes from SC meetings and teleconferences and other documentation.

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