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Universal Flu Vaccine

Final Report Summary - UNIVACFLU (Universal Flu Vaccine)

Influenza remains a threat to global health and a universal vaccine against pandemic influenza infections is much warranted. As the lead theme of this FP7 ITN project we have focused on the development of a broadly protective influenza vaccine. We have gathered a professional group of researchers in several European countries to train and educate 14 ESRs and 4 ERs in general concepts of vaccine development and influenza virus immunobiology, in particular. Currently licensed influenza vaccines generating neutralizing antibodies rely on insightful predictions of the next seasonal flu epidemic. However, these vaccines do not or poorly protect against pandemic flu infections. In addition, broadly protective vaccines have been found to require effective memory T cell immunity and rely less on neutralizing antibodies against the hemagglutinin and neuraminidas. Genetically reassorted influenza virus strains with a background in avian or swine influenza virus reservoirs present a high risk of a pandemic infection as people are naïve to these emerging virus strains. Intense research and clinical evaluation is, therefore, taking place to identify conserved B and T cell epitopes from the surface or structural proteins of influenza virus to generate broadly protective universal flu vaccines.
To this end the UniVacFlu consortium was established to build a European training platform that integrates young researchers in a highly innovative interdisciplinary process aiming to develop a universal influenza vaccine, which can provide cross-protection to existing and emerging influenza virus strains. The UniVacFlu consortium is a Marie Curie Initial Training Network of the FP7-People program running for 52 months with EU funding. Seven European partners from Sweden, England, Belgium, Germany, France, and Italy have just completed a successful training, research and educational program. The aim was to promote a next generation of skilled and highly competent young vaccine researchers and entrepreneurs. The highly ambitious training program was formed around the integrated and added values of the research groups in the consortium. This secured and provided full access to state-of-the-art technologies, excellent training laboratories and close contact with industry. The program started in November 2013 and since then the ER and ESR fellows have been involved in a series of workshops and training activities organized within and outside the consortium. The most important workshops and training modules organized by UniVacFlu are listed in the table below.

SEP’14 WS-1, Gothenburg, Sweden: Induction course and Science Communication & Personal Skills (UGOT)
MAY’15 WS-2/3, London, UK: Intro to Industry (Business & Commercial development & entrepreneurship/Research & Career Development workshop); Ethics in Research and Evidence based medicine
APR ’16
TC-2, Gothenburg, Sweden: Vaccines for next generation UGOT
FEB ‘17 TC-4, Milan, Italy: Advanced Immune Bio-Imaging
SEP ‘17 TC-3/WS-4, Ghent, Belgium: Nanomedicine and Medical Biotechnology

Enjoying the benefits of the UniVacFlu consortium platform the ESRs and ERs have developed into highly competent young professionals with excellent technical and theoretical skills making them highly employable with great career opportunities in academic, clinical as well as in industrial settings. The continuous output of oral and poster presentations at internal and external scientific meetings, participation at conferences and extensive outreach activities attest to the excellent training that the ESR and ER fellows have received. Their involvement in science communication to non-scientists via social media, blogs, videos and web sites are also important to mention in this context. Importantly, a large number of manuscripts have been or are submitted for publication in excellent peer reviewed journals. Two ESRs have defended their PhD thesis and at least 4 more of the ESRs are to defend their thesis within this year. The UniVacFlu consortium has been exceptionally successful in establishing a multidisciplinary European network platform for influenza vaccine research and development. It has received extensive contributions not only from the EU, but from other funding organizations helping to obtain the necessary capacity building and expertise for the development of a broadly protective universal influenza vaccine candidate.
The collective efforts of the consortium brought several competencies together to develop a candidate vaccine. The CTA1-3M2e-DD fusion protein was identified as a promising vaccine candidate and this molecule was therefore tested for protection in different formulations, including nanoparticle formulations, in the mouse model of influenza infection. It was found to stimulate broadly protective immunity against heterosubtypic influenza virus strains. The M2e- ectodomain of Matrix Protein 2 from influenza A strains is highly conserved among most strains. Moreover, the nanoparticle formulation was found excellent for hosting additional relevant antigens, such as the HA. Thus, the most efficacious vector tested included both the M2e-incorporated fusion protein and whole HA protein and their immunogenicity was greatly augmented by the CTA1-DD adjuvant included in the vector nanoparticle. Besides evaluating the nanoparticle formulation other innovative approaches, such as the microneedle vaccination technique was investigated further. An additional aspect of vaccine stimulated protection against influenza addressed whether changes in the gut microbiota affected the vaccine take following oral administration.

After completing their training the ESRs and ERs have acquired broad knowledge of vaccine research and development and were also given considerable insights into commercial vaccine manufacturing and testing. A unique opportunity to get to know one of the rare organizations for testing of influenza immunity and protection in a volunteer unit at hVivo/Retroscreen was also given during the program. This training spanned the whole range from discovery and innovative biology to industrial scale up and manufacturing. The ESRs and ERs have acquired skills that are highly relevant to Europe’s Health and Economy. Joint training activities and inter-laboratory visits have also established durable collaborations between the partner laboratories and the fellows and contributed to networking and effective introduction of the next generation of European influenza vaccine researchers. Finally, the program has been successful in identifying a mucosal candidate vaccine that does not only elicit efficient antibody responses, but also induces strong cellular immunity.