TRANSVAC2 is the follow-up project to its successful predecessor project TRANSVAC, the European Network of Vaccine Research and Development funded under FP7. The TRANSVAC2 consortium comprises a comprehensive collection of leading European institutions that propose to further advance with the previous initiative towards the establishment of a fully operational and sustainable European vaccine R&D infrastructure. TRANSVAC2 will support innovation for both prophylactic and therapeutic vaccine development based on a disease-overarching and one-health approach, thereby optimising the knowledge and expertise gained during the development of both human and animal vaccines. This will be achieved by bridging the translational gap in biomedical research, and by supporting cooperation between public vaccine R&D institutions of excellence, related initiatives and networks in Europe, and industrial partners. TRANSVAC2 will complement and integrate with existing European research infrastructures in both the public and private sectors. TRANSVAC2 will function as leverage and innovation catalyst between all stakeholders involved in vaccine R&D in Europe and -by providing integrated and overarching vaccine R&D services- will contribute to the development of effective products to address European and global health challenges, to controlling the burden and spread of infectious diseases, and reinforce the economic assets represented by vaccine developers in Europe. The impact of TRANSVAC2 will be maximised by two external advisory bodies. An independent Scientific & Ethics Advisory Committee will provide recommendations surrounding scientific-technical and ethical issues, whereas the coordination of TRANSVAC2 with other related initiatives and the further promotion of the long-term stability of a European vaccine R&D infrastructure will be supported by a Board of Stakeholders comprising representatives of policy and decision makers, industry associations and European infrastructures.

The European Regimen Accelerator for Tuberculosis (ERA4TB) has the explicit goal of developing a new combination therapy to treat all forms of TB starting from ~20 leads and drug candidates provided by EFPIA. Since details of these are as yet unavailable, we will implement an agile drug development algorithm that entails profiling and portfolio construction. Profiling involves characterisation and ranking molecules in preclinical studies comprising in vitro drug combination assays, hollow fiber and single cell analysis, innovative murine and non-human primate models, PK/PD studies, combined with biomarker discovery and non-invasive NIR or PET/CT imaging to monitor disease progression and response to treatment. Modelling, simulation and artificial intelligence tools will help progress compounds from early preclinical to clinical development and to predict drug exposure, human doses and the best combinations. After extensive preclinical profiling, selected compounds will enter portfolio development for first time in human tests and phase I clinical trials in order to ensure that they are safe, well-tolerated and bioavailable with negligible drug-drug interactions. If needed, formulation studies will be conducted to improve pharmacological properties. ERA4TB has assembled the best expertise and resources available in Europe, to build a highly effective and sustainable drug development consortium with a flexible and dynamic management system to execute the profiling and portfolio strategy, aided by clearly defined go/no-go decision points. The expected outcome of ERA4TB is a series of highly active, bactericidal, orally available drugs to constitute two or more new combination regimens with treatment-shortening potential ready for Phase II clinical evaluation. These regimens will be compatible with drugs used to treat common comorbidities, such as HIV-AIDS and diabetes, and should impact UN Sustainable Development Goal 3, namely, ending TB by 2030.

Antimicrobial resistance (AMR) is of great public health concern, causing numerous losses of lives worldwide and threatening to reverse many of the considerable strides modern medicine has made over the last century. There is a need to stratify antibiotic and alternative treatments in terms of the actual benefit for the patient, improving patient outcome and limit the impact on AMR. High quality, effective and appropriate diagnostic tests to steer appropriate use of antibiotics are available. However, implementation of these tests into daily healthcare practice is hampered due to lack of insight in the medical, technological and health economical value and limited knowledge about psychosocial, ethical, regulatory and organisational barriers to their implementation into clinical practice. VALUE-Dx will define and understand these value indicators and barriers to adoption of diagnostics of Community-Acquired Acute Respiratory Tract Infections (CA-ARTI) in order to develop and improve health economic models to generate insight in the whole value of diagnostics and develop policy and regulatory recommendations. In addition, efficient clinical algorithms and user requirement specifications of tests will be developed fuelling the medical and technological value of CA-ARTI diagnostics. The value of diagnostics will be tested and demonstrated in a unique pan-European clinical and laboratory research infrastructure allowing for innovative adaptive trial designs to evaluate novel CA-ARTI diagnostics. Close and continuous interaction with the VALUE-Dx multi-stakeholder platform provides for optimal alignment of VALUE-Dx activities with stakeholder opinions, expert knowledge and interests. A variety of dissemination and advocacy measures will promote wide-spread adoption of clinical and cost-effective innovative diagnostics to achieve more personalized, evidence-based antibiotic prescription in order to transform clinical practice, improve patient outcomes and combat AMR.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and is characterized by a high mortality of up to 30-40%. Treatment of sepsis was revolutionized by two steps that significantly decreased mortality: antibiotics and the intensive care units. It has been hoped that a third revolution, immunotherapy, would further improve outcome of sepsis, but this hope did not materialize. This was due to the incompletely understood pathophysiology, and the heterogeneity of the immune status in different sepsis patients. We propose that while both overinflammation and immunoparalysis are important, they are present in individual sepsis patients.The mission of the present project is to design and perform a proof-of-concept clinical trial of personalized immunotherapy in sepsis, and within this clinical trial, to develop a next-generation theranostics platform for the design of future personalized immunotherapy trials in sepsis. This theranostics platform would be based on an integrated, multidimensional systems biology analysis of omics-based datasets, to identify biomarkers, clinical endotypes, and therapeutic targets for precision medicine approaches. In order to achieve the mission proposed, several complementary aims will be pursued: Aim 1: To design and perform a large personalized immunotherapy trial in sepsis patients, that can provide a clinical answer towards the usefulness of currently employed immunotherapies for sepsis. Aim 2: To chart host genome, epigenome, transcriptome, metabolome and microbiome in at least 180 sepsis patients enrolled in Aim 1 over a defined time course. Aim 3: To use a theranostics approach based on the data provided by Aim 2 to design novel personalized immunotherapeutic strategies. Aim 4: To integrate the clinical and psychological aspects involved when introducing novel immunotherapies for infections in the health care systems of European countries, building bridges with the patient community.

TRANSVAC-DS project further builds on the outstanding success of EC-funded projects:TRANSVAC1 and TRANSVAC2 and proposes the establishment of a truly sustainable European vaccine infrastructure, which will build upon the lessons learned, activities and achievements of the TRANSVAC1/2 projects. Two infrastructure projects -TRANSVAC1 and TRANSVAC2- have been funded by the European Commission which -through the provision of state-of-the-art scientific-technical vaccine development services, technical training, and innovative vaccine research and development- have provided very significant support to European vaccine researchers and developers. Support has been, and is being provided to the development of human and veterinary prophylactic and therapeutic vaccines. The twenty-five partners in the TRANSVAC-DS consortium that will contribute to the outcome of the project represent ten EU Member States and Associated Countries and include leading organisations from the European vaccine R&D field. The main output of TRANSVAC-DS will be a conceptual design report that will describe in detail the maturity of the concept and be the basis for the establishment of a permanent and sustainable vaccine infrastructure of direct relevance to and benefit for Europe and further afield. As part of the design report, a five-year business plan will be delivered together with an implementation plan that will guide the further establishment of a sustainable European vaccine infrastructure.