Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Therapeutic TriMix / mRNA based Vaccine in Chronic HIV-1 Infected Patients Receiving Antiretroviral Therapy (IHIVARNA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Spain,Belgium,Belgium,Netherlands,Belgium
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2013-12-01
End date: 2017-11-30
Duration (months): 48.0
Total project cost (EUR): 7826907.2
EU funding (EUR): 5984720.0
Participants: 8
Project status: CLOSED

To find a therapy alternative to cART for life is one of the hot topics of investigation in HIV field. Therapeutic vaccination seems to be the best option. We have reported in a double-blind placebo controlled study some of the best, most solid data showing that HIV-1 specific immune responses elicited by therapeutic dendritic cell (DC) vaccines pulsed ex vivo with inactivated autologous whole virus could significantly change pVL set-point (mean peak drop of -1.2 log10 copies/ml). Similar efficacy has been found in a preliminary non controlled clinical trial using DC electroporated with mRNA encoding autologous HIV-1 antigens. However, the logistics of developing a specific vaccine by ex vivo manipulating autologous DC for each patient may be prohibitive. Therefore, we propose that in vivo targeting of DC by direct administration of a rational designed HIV mRNA encoding immunomodulating proteins might be an attractive alternative to target DCs in situ. Our candidate is highly innovative: 1. It is a mRNA based immunogen: it is expected to have a good safety profile, it is classified as nongene therapy by the American and German authorities, is easier to produce and to store regardless of the encoded antigen and is not restricted to a defined HLA type of individuals. 2. The HIV antigen encoded by mRNA has been selected with a rational design: based on our previous works selecting viral targets of protective HIV-1 specific T cell responses in 3 large cohorts of HIV infected individuals. 3. The candidate includes TriMix to target DC in vivo: our data suggest that mRNA encoding a mixture of antigen presenting cells activation molecules (CD40L, a constitutive active variant of TLR4 and CD70) significantly enhanced the induction of antigen-specific T cells. If this candidate would be able to obtain the functional cure in at least a proportion of patients it could be applicable to developing countries and would improve the care and cost of HIV infection.

Keywords: hiv functional cure,mrna based immunogen,clinical trial,hiv antigen eliciting t cell responses.
InFLUenza virus UNIVersal VACcine development program (FLUNIVAC)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,Germany,Belgium,Sweden,Netherlands,Netherlands,Germany
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2013-10-01
End date: 2018-01-31
Duration (months): 52.0
Total project cost (EUR): 6973633.0
EU funding (EUR): 5066881.0
Participants: 8
Project status: CLOSED

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. 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.

Keywords: universal influenza vaccine,broad-protective and long-lasting immunity,recombinant mva,antibody and t-cell induced immune response
PHYSICAL ACTIVITY THROUGH SUSTAINABLE TRANSPORT APPROACHES (PASTA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: Austria,Switzerland,Belgium,Sweden,United Kingdom,Italy,Switzerland,United Kingdom,Germany,Belgium,Germany,Spain
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2013-11-01
End date: 2017-10-31
Duration (months): 48.0
Total project cost (EUR): 6594485.4
EU funding (EUR): 5122539.0
Participants: 16
Project status: CLOSED

This project focuses on the systematic promotion and facilitation of active mobility (AM) (i.e. walking and cycling including the combination with public transport use) as an innovative approach to integrate physical activity (PA) into individuals’ everyday lives. In contrast to sports or exercise, AM requires less time and motivation, since AM provides both convenience as a mode of transport, and a healthy lifestyle. As such it has potential to reach parts of the population which have not been receptive to the appeals and benefits of sports and exercise. The objectives of the project are the following: • The project will review the literature on AM and identify innovative measures and systematic initiatives to promote AM as well as traffic safety interventions. • A longitudinal study will be conducted to evaluate the ongoing AM initiatives combined with traffic safety interventions to better understand correlates of AM and their effects on overall PA, injury risk and exposure to air pollution. • An improved user-friendly tool for more comprehensive health impact assessment (HIA) of AM will be developed. • The tool will be applied to AM behavior observed in the case study cities and allow the assessment of health and economic impacts of measures. • The project will also produce a compendium of good practices of AM promotion aimed at decision makers, implementing authorities, businesses, civil society organizations and end users. • Findings and progress reports will be communicated to diverse target audiences, including policy makers, practitioners, researchers and end-users, through a number of media, i.e. reports, journals, brochures, web-content, workshops and presentations.

Keywords: active mobility,physical activity,daily life,walking,cycling,health impact assessment
Combinatorial immunization strategy to educate the immune system towards cross recognition and coverage against antigenic drift in seasonal influenza virus exposure (EDUFLUVAC)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Portugal,Italy,Netherlands,Netherlands,United Kingdom,Germany,Switzerland
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2013-11-01
End date: 2017-10-31
Duration (months): 48.0
Total project cost (EUR): 6088877.0
EU funding (EUR): 4647149.0
Participants: 7
Project status: CLOSED

As current influenza vaccines only afford limited protection against seasonal as well as pandemic influenza, and require regular updating, 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 health care priority in both industrialized and low and middle income countries. EDUFLUVAC aims to develop an influenza vaccine that educates the immune system to recognise common influenza epitopes, using a combination of influenza haemagglutinin (HA) antigens delivered on a single virus-like particle. This vaccine concept, using the proven, modern technology of baculovirus VLPs will enable enhanced cross linking of B-cell receptors and favour induction of B-cell responses against common epitopes essential for long-lasting cross recognition and protection. 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. A similar approach for developing a novel vaccine for pandemic use will be tested. The knowledge generated will provide 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 for an economically viable large scale production platform for influenza vaccine which, in the event of a pandemic, can manufacture rapidly high quantities of vaccine. All industrial partners (including two SMEs) will benefit from the compilation of the regulatory dossier for transfer to larger vaccine companies and the deeper knowledge integration emanating from EDUFLUVAC in a $2.8 billion global annual influenza vaccine market.

Keywords: vaccine,influenza,vlp,baculovirus,insect cells,multivalent,mice,ferret,nhp
Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases (PDE4NPD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,United Kingdom,United Kingdom,Germany,Spain,Egypt,Belgium,Brazil,Netherlands,Germany,United Kingdom
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2014-03-01
End date: 2018-02-28
Duration (months): 48.0
Total project cost (EUR): 7799246.76
EU funding (EUR): 6000000.0
Participants: 11
Project status: CLOSED

This project aims to unite global efforts to target the highly druggable class of enzymes called cyclic nucleotide phosphodiesterases (PDEs) in the fight for neglected parasitic diseases (NPD). It will establish a drug discovery platform, PDE4NPD, that combines phenotypic screening with efficient target-centric drug discovery, including target validation, various strategies for compound screening, PDE hit and lead optimization, safety and toxicology assessments and evaluation of anti-parasitic activity. The platform will make use of the target class expertise that the participating SMEs have gained when developing drugs for human and parasite PDEs, while all public partners offer proven experience in the field of NPD. The SMEs will adopt and progress existing PDE inhibitors that are in different stages of the drug discovery pipeline (i.e., target validation, hit and lead optimization). The current portfolio of inhibitors have clinical potential for treating sleeping sickness, Chagas' disease and leishmaniasis. Finding novel hits and leads for the PDEs that are associated with helminth diseases is also foreseen. The platform is open for targeting other NPD, and a broad panel of phenotypic screens (including malaria) is available to test PDE inhibitors. The phenotypic screening is performed by world-renowned groups, including two institutes in endemic countries. By capturing human and parasite PDE-related data in annotated chemogenomics databases, PDE-4-NPD will achieve the knowledge accumulation that is typical for target-centric approaches, thereby making the NPD drug development more efficient and enabling the SMEs to take advantage of the molecular understanding that is key for developing new medicines. The PDE4NPD platform constitutes an ideal basis for creating fruitful collaborations with both public and private partners word-wide.

Keywords: neglected diseases,parasite,sme,drug discovery,pde inhibitors,target-centric,phenotypic,screening,in vivo,clinical,chemogenomics,chagas',sleeping disease,helminth,malaria,leishmaniasis
Local Immunomodulation around implants by innovative auxiliary hydrogel-based systems encapsulating autologous and phenotype controlled macrophages (IMMODGEL)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Germany,France,Germany,United Kingdom,United States,Estonia,Czechia
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2013-10-01
End date: 2017-09-30
Duration (months): 48.0
Total project cost (EUR): 7468527.13
EU funding (EUR): 5851316.1
Participants: 10
Project status: CLOSED

IMMODGEL aims to identify adverse immune reactions to dental and larynx titanium implants and to develop a novel therapeutic strategy to significantly decrease the implant and medical device failure caused by these reactions via design of an innovative immunomodulatory system. The system will be designed to be fixed to an implant via an adhesive polyelectrolyte multilayer and control the immune response by autologous, phenotype modulated macrophages encapsulated in a hydrogel. The auxiliary nature of the design allows it to be adjusted to any implant, medical device or transplant. IMMODGEL will apply complex systems immunology, epidemiology, and functional approaches to identify key adverse immune reactions caused by implants and detrimental macrophage phenotypes around titanium implants. This will be used to establish the optimal biomaterial composition and cytokine delivery system for the immunomodulatory hydrogel design to revert macrophage-induced inflammatory reactions (M1) to the optimal tolerogenic and healing reactions (M2). Long-term fixation of the desired M2 phenotype will significantly decrease the level and duration of implant-induced inflammation, and optimise healing phase. The interaction of implants and medical devices with the immune system will be modelled to develop a “Foreign Body Response on-a-chip” to predict patient’s specific responses to implant materials and modify the immunomodulatory hydrogel accordingly, as a step towards personalized implants with minimal adverse reactions. The gels will be incorporated to engineered tissues for validation. Validation of the approach will be performed in vivo in animal models. Significantly suppressed inflammatory responses and optimal tissue remodelling and healing around titanium implants is expected. The key innovation will be the development of IMMODGEL as an auxiliary system to improve the outcomes of implantation and reduce the cost of implant complication and related medical costs in Europe.

Keywords: macrophage,systems immunology,phenotype control,cell encapsulation,hydrogels,bioprinting,immunomodulation,phenotypic plasticity,titanium,implants,dental,larynx
MULTISCALE APPROACH TO THE IDENTIFICATION OF MOLECULAR BIOMARKERS IN ACUTE HEART FAILURE INDUCED BY SHOCK (SHOCKOMICS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Italy,Spain,Switzerland,Belgium,United States
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2013-10-01
End date: 2017-09-30
Duration (months): 48.0
Total project cost (EUR): 6703316.95
EU funding (EUR): 5174001.0
Participants: 11
Project status: CLOSED

The management of cardiovascular stability in shock patients is of paramount importance in critical care. New, cutting edge knowledge is necessary to overcome the shortcomings of available therapies, in order to cope with the challenges that anesthesiologists, intensive care specialists and emergency physicians face when dealing with shock patients. Current therapies are targeted to reduce symptoms of shock and multiple organ failure, but they are unable to target the root cause or to act at the “beginning of the cascade”, because of the lack of a model explaining the molecular basis of shock induced tissue injury and ensuing multiple organ failure. Hence, the effectiveness of anti-hypotensive interventions such as fluid resuscitation is limited. Fluid may restore blood pressure within minutes, but complications such as pulmonary edema may arise on a longer time scale in patients who are unresponsive to fluid infusion, and cause more severe stress to the patient’s hemodynamic stability, respiratory efficiency, and immune system. This proposal seeks to shed light on the molecular trigger of acute heart failure in association to shock, in the presence of uncontrolled proteolytic activity, in order to identify inflammatory mediators and markers which are activated in shock, through a systematic analysis of expression levels of genes and their protein products, and novel targets for the delivery of new therapies, necessary to overcome the limitations of current ones.

Keywords: shock,heart failure,inflammation,biomarkers,cardiovascular instability,omics approach,metabolic pathways,proteolysis
EURO EWING Consortium – International Clinical Trials to Improve Survival from Ewing Sarcoma (EEC)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,Belgium,France,Germany,United Kingdom,Netherlands,France,France,Spain,Spain,Austria,Italy,Sweden,United Kingdom,Germany,Germany
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2013-10-01
End date: 2019-09-30
Duration (months): 72.0
Total project cost (EUR): 7428274.74
EU funding (EUR): 5697830.9
Participants: 21
Project status: CLOSED

Ewing Sarcomas (ES) are fatal, rare bone cancers particularly affecting young people. About 60% of patients achieve long term survival with current treatment but there has been no improvement in this proportion for 25 years. Treatment is unsuccessful because chemotherapy fails to prevent the development of, or to effectively treat established, metastases. In addition, of the 600 new cases of ES occurring in the EU each year, less than half will receive treatment ‘appropriate’ to deliver the most favourable outcome. The EUROEWING Consortium (EEC) is a coalition of clinical study groups bringing together the most active clinicians and scientists in Europe dedicated to improving survival from ES. This initiative can achieve this through an integrated programme of investigator-driven, inclusive clinical trials that are rigorously designed, conducted, analysed and reported, and underpinned by complementary embedded translational research. These include i) a first line randomised study in patients of all ages with ES which defines standards of care to prevent development of metastases and serves as a backbone for implementation of new agents, and ii) a randomised study of current second line chemotherapy in patients of all ages with ES which will serve as a platform for testing of new agents. Companion studies in association with these trials will be performed investigating tumour biology, underlying causes of differential response and toxicity, and other biomarkers. The programme will be supported by new initiatives for the involvement of patients in research planning and operation. Through collaborative working, the EEC will provide ES patients with greater access to clinical trials, allow efficient acquisition of knowledge and deliver clinically meaningful results within the lifetime of the grant, thereby contributing to improved survival from ES.

Keywords: ewing sarcoma (es),metastasis,investigator-initiated,translational research,survival
Upscaling human insulin-producing beta cell production by efficient differentiation and expansion of endoderm progenitors (HUMEN)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Denmark,Germany,United Kingdom,France,Sweden,Germany,France,Germany,Netherlands
Call:  (FP7-HEALTH-2013-INNOVATION-1, 2013)
Start date: 2014-01-01
End date: 2017-12-31
Duration (months): 48.0
Total project cost (EUR): 7860730.2
EU funding (EUR): 5962644.0
Participants: 9
Project status: CLOSED

Despite progress in producing beta cells from human pluripotent stem cells (hPSCs) in recent years, full differentiation cannot be obtained in vitro. The HumEn project hypothesises that a fundamental understanding of the coupling between endodermal progenitor expansion and differentiation is relevant for elucidating how to a) generate glucose-responsive beta cells from hPSCs in vitro, and b) generate sufficient number of beta cells to meet future clinical needs in cell therapy in diabetes. Thus, the overall aim of HumEn is to identify, understand, and expand human endodermal progenitors as a consistent and renewable source of cells for pancreatic beta cells differentiation. We will focus on precursors from two stages of pancreatic differentiation; anterior definitive endoderm (ADE) and pancreatic endoderm (PE) progenitors, providing mechanistic insight into the signalling pathways and downstream targets that control their expansion and functional maturation into human beta cells. Rigorous in vitro (regulated insulin-release) and in vivo (protection against experimentally induced diabetes in mice) testing of insulin-producing cells will ensure a functional end product. The consortium proposes to address these problems by a unique combination of models and experimental approaches, including genetic, surface/biomaterial screens (3D), and cell surface antibody screens as well as cell signalling-to-transcription factor/chromatin effectors. In the end, HumEn aims to deliver a reliable and scalable protocol for directed differentiation of hPSCs into bona fide beta cells. The results of the project will not only provide answers to fundamental questions, but also deliver new concepts and knowledge of general importance for coordination of cell cycle progression and regulation of cell fate specification in stem cells/progenitors. HumEn is highly innovative and carries excellent potential for translational output.

Keywords: human pluripotent stem cells,progenitors,anterior definitive endoderm,pancreatic endoderm,pancreatic beta cells,proliferation,differentiation,cell signalling,mechanotransduction,extracellular