EDUcate inFLUenza VACcine


Current influenza vaccines afford only limited protection against seasonal as well as pandemic influenza.  As influenza viruses can accumulate three-four amino acids substitutions per year and frequently change antigenically to escape population immunity, vaccine composition has to be updated and vaccines need to be administered annually.  As a consequence, persistent monitoring and selection of viruses, production, formulation and conduct of clinical trials to evaluate safety and immunogenicity of the new vaccines are necessary every year.  A major shortcoming is therefore that the relatively long production time results in a vaccine that does not always have a sufficient antigenic match with the epidemic strain.  

A significant advance in human infectious disease research would be the development of a new generation influenza vaccine that stimulates production of a robust, broadly neutralising antibody (bnAb) response, not only to drifted variants of seasonal influenza viruses, but preferably also to different influenza A virus subtypes that regularly infect birds and mammals, and may be the basis of future influenza pandemics.  Thus, the development of a “universal” influenza vaccine that can provide broad coverage against different strains within a subtype or even across subtypes has become a key public health priority in both industrialised and low and middle income countries.


In order to address the problem of antigenic drift and annual vaccine reformulation, the EDUFLUVAC Consortium, funded by the European Commission (EC) 7th Framework Programme (FP7), proposes to develop a combinatorial immunisation strategy to educate the immune system towards cross recognition and coverage against antigenic drift in seasonal influenza virus exposure.  

To achieve this goal, EDUFLUVAC aims at developing a novel influenza vaccine candidate encompassing a combination of multiple influenza haemagglutinin (HA) or neuraminidase (NA) antigenic variants within a single (sub)type.  This vaccine concept, using the proven, modern technology of baculovirus-derived virus-like particles (VLPs), is expected to elicit a broad neutralising immunity that will confer longer-lasting and broader protection against multiple strains of influenza virus.

The mechanism underlying the broadening of antibody responses is the increased relative concentration of common epitopes diluting out strain specific epitopes.  This will be achieved by testing the ability of a combination of historic HA variants to protect against a variety of modern isolates.  The overall strategy of the EDUFLUVAC project will be to select HA and NA antigens representing antigenic drift within relevant (sub)types and generate baculovirus vectors for expression of one or more HAs.  VLPs will be tested in immunological studies in mice for further selection of VLP vaccine candidates.  Proof of principle of the EDUFLUVAC strategy will then be demonstrated in challenge studies in ferret and non-human primate (NHP) models.  Furthermore, an optimised process suitable for current Good Manufacturing Practice (cGMP) production of VLPs will be developed.  The project will take note of new influenza vaccine regulatory guidance, and will be geared towards the development of a complete Investigational Medicinal Product Dossier (IMPD) ready for transfer into cGMP production of vaccine batches for early phase clinical testing.  Finally, the knowledge generated will be disseminated and relevant networking will be addressed, e.g. via a workshop series.

Hence, EDUFLUVAC aims at providing proof of principle in relevant animal models for an influenza vaccine that does not have to be updated annually, does not have to be manufactured on an annual basis, and will not require an annual vaccination campaign.  It will also provide an economically viable large scale production platform for influenza vaccine which, in the event of a pandemic, could manufacture high quantities of vaccine rapidly.

Major Milestones

  • Selection of HA and NA antigens representing antigenic drift within the H1, H3 and B (sub)types: Q4 2013
  • Generation of baculovirus vectors for expression of one or more HAs or NAs: Q2 2014
  • Production of VLPs for immunological studies in mice: Q4 2014
  • Evaluation of VLPs in mice for immunogenicity and efficacy: Q3 2015 
  • In process assays for product characterisation - assays developed and qualified for technology transfer: Q3 2015
  • Production of VLPs for ferret and NHP immunological studies: Q1 2016
  • Evaluation of VLPs in ferrets and NHPs for immunogenicity and efficacy: Q3 2017
  • Process development to enable smooth transition into current cGMP production of VLPs and technology transfer dossier: Q4 2017

Participants at the EDUFLUVAC Kick-off meeting, Heidelberg, November 2013

Participants at the EDUFLUVAC Kick-off meeting, Heidelberg, November 2013