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InFLUenza virus UNIVersal VACcine development program (FLUNIVAC)
Date du début: 1 oct. 2013, Date de fin: 30 sept. 2017 PROJET  TERMINÉ 

Effectively protecting the general population from seasonal and pandemic influenza has proven to be a challenge, since influenza viruses continue to escape from and evade immunity. Current influenza vaccines fail to provide long-lasting and broad protection against multiple strains of influenza. For the development of a universal influenza vaccine, we have to “do better than Nature”, since even natural influenza virus infections fail to induce broad protective immunity. To induce broad-protective and long-lasting immunity an influenza vaccine should therefore be directed to conserved viral proteins or regions thereof that are insufficiently exposed upon natural infection. FLUNIVAC is a SME-targeted collaborative research project that aims to develop a candidate influenza vaccine based on recombinant MVA expressing both antibody and T-cell response-inducing proteins, ready to commence Phase I clinical trials within 4 years. We will generate recombinant MVAs that express nine conserved (regions of) influenza A virus proteins (surface proteins HA, NA, M2e, internal proteins M1, NP, NS1, and the polymerase proteins PB1, PB2, PA). These proteins are targets for both antibody and T-cell mediated immune responses, since the induction of solely one of both affords only modest protection against infection with influenza viruses of heterologous subtypes. These recombinant MVAs will be tested for their capacity to induce the desired broad-protective immune response individually and in selected combinations in vivo. In parallel, MVA-induced immune responses will be tested for their longevity and boostability as compared with those induced with adjuvanated vaccine preparations. Furthermore, the MVA platform will be optimized in terms of: i) kinetics and extent of protein-expression of the MVA vector to optimally activate the respective arms of the immune system; ii) a viable unified production process, independent of embryonated chicken eggs, will be designed and implemented.



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