Final Report Summary - EURIPRED (European Research Infrastructures for Poverty Related Diseases)
Executive Summary:
EURIPRED is a collaborative infrastructure FP7 project coordinated by the Project Management Team at MHRA NIBSC. During the last four years of operations, EURIPRED has demonstrated the feasibility of integrating international resources into a single specialised infrastructure to support European HIV, TB, malaria and hepatitis B/ C virus studies from early drug, vaccine and microbicide discovery to clinical trials. The project achieved its goals by creating partnerships between European scientists and international research teams from disease endemic countries and strong collaborations between industry and public sector research. This has brought international resources and facilities together to develop cost-effective products/ reagents for the European scientists. EURIPRED has successfully integrated worldwide resources to allow European access to shared biological materials and research reagents.
EURIPRED aims to develop, characterise and make available a selection of reference reagents/ standards for access through Transnational access (TNA). This has been achieved by partners from various research institutes and biotechnology companies working together. The six Biobanks within the EURIPRED project have collected more than 1000 new clinical samples from selected patients from six different countries including the Kenya, Russia, China, India, Spain and UK. These biological materials are well characterised and some of them have been used to generate novel research and reference reagents. About 300 new research and reference reagents have been produced, characterised and made available through TNA during the project life. Most of the materials have been deposited at the NIBSC Centre for AIDS Reagents Repository (CFAR) where they will be held securely under the ISO9001 quality system and made available to researchers under Material Transfer Agreements.
One important measure of success of the project is the provision of materials and services to researchers through the EURIPRED TNA process. Free access to all EURIPRED services have been provided to 41 scientific research projects across various infectious disease areas including HIV, tuberculosis, malaria, hepatitis and emerging viral infections. The end user applications were selected through a scientific evaluation process conducted by a group of experts in the relevant areas based on scientific excellence, feasibility and impact.
Joint research activities have been focussed on the assay harmonisation of a series of immunological assays used in vaccine studies across different pathogens. Some clinical samples were used to optimise the final harmonised protocols and final Standard Operating Procedures (SOPs) of assays were prepared and made available on the EURIPRED website for wider access to the scientific community. The process of harmonisation and data obtained will be published in open access, peer-reviewed journals.
EURIPRED provided three web-based and five on-site laboratory trainings. A number of webinars and a series of SOPs and protocols for scientific research are available online via the EURIPRED website. The Virtual Institute platform (http://viprd.eu/) has been developed and structured with various functionalities. Information has been populated on this Virtual Institute by partners during the project life.
Project Context and Objectives:
HIV/AIDS, Tuberculosis (TB) and Malaria alone account for more than six million deaths worldwide every year. Despite substantial efforts made in recent years, Poverty Related Diseases (PRDs) are still spreading. New therapeutic interventions are therefore urgently required to combat PRDs. The existence of a well-developed HIV/ TB/ malaria infrastructure presents a prime opportunity to address other sexually transmitted diseases such as viral hepatitis efficiently and effectively. The overall goal of the EURIPRED is to coordinate and integrate international resources into a single specialised infrastructure to support European HIV, TB, malaria and hepatitis B/ C virus studies from early drug, vaccine and microbicide discovery to clinical trials. This will be achieved by creating partnerships between European scientists and international research teams from disease endemic countries and strong collaborations between industry and public sector research. Although vaccines, drugs and microbicide research activities are being conducted in the European Union (EU), there is no single European infrastructure that brings international resources and facilities together to develop cost-effective products/ reagents for the European market. To underpin this need, EURIPRED will integrate worldwide resources to allow European access to shared reagents. This integrated approach will strengthen international cooperation, increase research capacity in EU and developing countries and significantly contribute to the European Research Area (ERA). By minimising fragmentation and duplication of research efforts and pooling fragmented resources EURIPRED can improve European research efficiency and effectiveness.
Delivery of these goals will be achieved through the following scientific and technical objectives:
1) Strengthen, broaden and exchange knowledge and know-how between partners
2) Promote and enable communication with other stakeholders and projects by networking
3) Provide the scientific community with transnational access to participant-owned European and international resource infrastructures
4) Horizontally collaborate with infrastructures and services within the consortium
The consortium is supported by a strong collaboration between the partners with the overall goal of enhancing user access to world-level research infrastructures, thanks to their complementarities. New products such as clinical isolates representative of HIV, Hepatitis B and C virus, M. tuberculosis and
Plasmodium falciparum strains circulating within Europe, China, India, Russia and Africa will serve as important sources for interdisciplinary research, and thus contribute directly to scientific European excellence in a competitive research and economic domain. The partners involved in clinical studies of TB, vaccine clinical trials and basic R&D are placed to provide unique access to a wide range of materials, that will drive both clinical and preclinical development of vaccines as well as underpin and strengthen basic research on infection, immunology and pathways to new interventions. Proteins, peptides, and complex compounds such as defined glycolipids are critical to undertaking fundamental research in this important infectious disease. Wider access to such materials to the European scientific community will provide a much strengthened reagent and materials infrastructure that will allow novel and cross-linking strategies to be developed
The project consists of three main streams of activities including networking activities (WP1, 2 & 7), joint research activities (WP3, 4 & 5) and transnational access (WP6). The project management is performed in WP8.
Project Results:
Work Package 1 - Resource Management and Quality Assurance
One main goal of EURIPRED is the collection of new specimens of HIV, TB, Malaria and viral hepatitis through the collaboration of various biobanks worldwide. The partners involved in WP1 brings together an extensive range of technical platforms, protocols, know-how and pooled expertise on quality assurance, database set-up and management and biobanking of clinical and research materials. This resource provides guidance, expert knowledge on reagent and data acquisition, quality control testing, storage and international specimen transport. Furthermore the biobanks have worked together to harmonise and standardise processes for reagent management, testing and transport. KCL circulated up-to-date standard operating procedures (SOPs) describing the process of sample collection, storage and blood fractionation. In addition, an Ethics Advisory Committee (EAC) has been created and overviewed the ethical aspects of the project. In order to ensure quality assurance during the distribution of reference reagents/ standards developed by WP4, NIBSC-CFAR has renewed the accreditation to ISO9001:2008 for receipt, storage and distribution of reagents. The collection and analysis of clinical samples generate a large amount of data. In order to centralise this information, UNICUM has developed the IT structure of the Virtual Institute for Poverty Related Diseases (VIPRD). The VIPRD is a web-based platform aiming at gathering and making available a central biobanks registrar for the EURIPRED project, as well as promoting scientific interactions through network functionality.
During last period of the project, all deliverables have been completed. In addition, the ongoing harmonization of biobanking activities has continued. We have a well-managed and accessible reagents and clinical materials available to the broader scientific community thereby fulfilling the legacy aspects of the EURIPRED project.
Work Package 2 - Networking with other Groups and Projects
The overall goal of WP2 is to network with international research programmes and projects to establish a wider network that will allow integration of HIV, Hepatitis, TB and Malaria research within Europe and beyond and promote the EURIPRED project. During the first reporting period was to perform an inventory of already existing initiatives and research activity in the field of poverty related diseases (HIV, HBV, HCV, TB and malaria). The WP2 partners generated a survey to be filled in by all EURIPRED researchers aiming at collecting information on collaboration/ network among EURIPRED partners in the form of a catalogue. Such overview was disseminated to all partners to foster interactions among the EURIPRED partners and beyond. Analysis of the respondent answers helps identifying gaps and needs for joint research activities and potential for new collaborations. The output has been combined into a strategic agenda. Ultimately the networking activities undertaken will improve and globalize research culture leading to a more interdisciplinary approach and solution to scientific questions.
During the second period, we aimed at pursuing the effort to bring awareness on the EURIPRED project and TNA opportunities together with integrating the Virtual Institute (VI) under development in the networking strategy. In addition to the pre-existing links and networks via the project partners, the partners aimed at consolidating the resources available via the catalogue already produced. Special attention was given in identifying gaps in the catalogue and missing key stakeholders/ initiatives in the poverty related diseases (charities, foundations, etc). An effort was made in identifying the key persons to be approached to initiate communication and foster visibility of the project and bring awareness. In addition, the final architecture of Intranet/ Extranet platforms of the VI was built. All developed functionalities were tested, installed and used in WP2 for strengthening communication within the partners and with external networks and projects. Access to the extranet has been provided to 42 external institutions (MS 13 new collaboration set-up) and special attention has been given by MHRA to foster new collaborations (visit Pasteur Institute in Shanghai, 24 October 2016). A strategic agenda was developed to provide an integrated overview of the activities to be performed within the WP2 networking.
The last period of the project aimed at ensuring the visibility of EURIPRED and to give a final push towards utilisation of the TNA offerings remaining on the project. In the meantime, the fine tuning of the VI functionalities was undertaken for further integration of the VI into the networking strategy. A final update of the catalogue was undertaken to reflect the new networking opportunities that came from newly funded projects (D2.4). A special effort was made in reaching out to all identified organisations, charities and project coordinators listed in the catalogue to ensure the visibility of the project.
Work Package 3 - Patient recruitment, Sample selection and Characterisation of Biological Materials
The objective of WP3 is to establish a comprehensive biobank of HIV, HBV, HCV, malaria and M.tb for trans-national access from the unique population and to provide the biological materials for the development of novel reagents. The patient recruitment, sample selection and characterization of biological materials are the key process for ensuring the smooth implementation of the project. This work package aims to the collection and characterization of pathogens from multiple sites and has been expanded the collection by assembling new cohorts to capture contemporary circulating strains of HIV, HBV, HCV, malaria and M.tb from the UK, India, China, Russia, Spain and Kenya, characterize the genetic and biological characteristics, and then supply biological materials for primary use in the EURIPRED project.
From the beginning of the project, KCL-UK has collected 356 HIV+ samples, KCL-India 74 HIV+ and 122 TB+ samples; NCAIDS 50 HIV+ samples; Gamaleya 70 HIV+, 39 HIV-Mtb and 77 HIV-HCV+ samples; KEMRI 100 HIV-Mtb and 28 HIV-Malaria samples; ISCIII 90 HIV+ samples. As the timing of work packages, biological and epidemiological properties of the newly and previously collected samples from all sites were characterized by the collection institutes including viral load, CD4 counts, pol gene, the neutralizing activities and so on. A total of 76 HIV-1 viruses were isolated, 31 viruses from Chinese patients and 5 isolates from Russian patients and 40 from Spanish patients. Full length genomic sequences, specific features, co-receptor usage and phylogenetic analyses of new and previous HIV-1 isolates were analysed. HIV whole genome of plasma samples from India and 79 Mtb whole genomes were identified by KCL-India. A PCR to initiate sequencing of the Gag region of HIV was established by KCL-UK, which had obtained the cohort 70 sequences. In addition, MHRA-NIBSC had set up a protocol to identify the sequence of HIV by RT-PCR +NGS, and had performed it on EURIPRED samples collected. Library design PepMix pools were finished for 3 Antigens (2 HIV - gag & nef and 1 HBV - C-protein), and library design Peptide Microarrays were finished for 2 Array-Libraries (HIV & HBV) by JPT.
For the period M37-M48, the patient recruitments were replenished with 121 Russian patients with 21 HIV/HCV co-infections and 63 HIV/TB co-infections, 18 Spanish HIV patients infected with viruses of subtype B, non-B subtypes and circulating recombinant forms (CRFs). The samples and the patient characteristics were collected, and the collected samples were characterized by collection institutes including viral load, CD4 counts, the neutralizing activities, and so on. As the timing of work packages, the dominant or novel viruses were isolated from the samples collected from China, Russia and Spain, of which the HIV-1 near full-length genome was amplified and sequenced. The co-receptor usage of novel/dominant HIV-1 isolates was also determined by the collection sites. All the samples including the plasma/serum samples, HIV-1 primary isolates and PBMCs, had been sent to NIBSC repository from the multiple sites of WP3, 110 HIV positive samples from Gamaleya, 130 HIV samples from ISCIII, 50 HIV positive samples (1038 tubes for plasma) and 44 HIV clinical isolates(150 tubs) from China, respectively. Gamaleya evaluated the anti-HIV activity of anti-MTB drugs in Russian patients and discovered two anti-TB drugs (Linezolid and Isoniazid) showed dual inhibitory effect against the two infections (TB and HIV). In addition to the libraries for peptide microarrays towards the pathogens HIV, HCV, HBV and M.tb the library for Plasmodium falciparum and P. vivax and an additional HIV library for sequence information gathered in the EURIPRED project were designed by JPT. To support the WP3 task 3.2 on sample characterisation of samples, MHRA-NIBSC amplified 30 HIV envelope genes from clinical samples collected through EURIPRED with various genetic background including subtypes B, C, F, G, CRF01_AE, CRF02AG, CRF03_AB, CRF05_D/F, CRF07_BC, CRF08_BC, CRF35_AD and CRF43_02G, clones it and tested their functionality.
Work Package 4 - Development and Evaluation of Reference Reagents
WP4 aims to develop, characterise, and make available a selection of reference reagents/ standards for access through Transnational Access (TNA). Reference reagents developed through this platform will be tested for functionality, and protocols and final reference reagents specifications will be shared. In the first six months, the WP partners identified and agreed on the selection criteria for biological materials for development of reference reagents (Task 4.1) as well as for the priorities for the development of reference reagents/standards (Task 4.2).
During the period until month 48 KCL-India has sequenced and characterised 19 extensive drug resistant Mtb strains for mutations in known T cell epitopes. In total 79 Mtb whole genomes have been scanned for mutations in CD4 T-cell epitopes. The screen of 1101 T cell epitopes revealed 138 new mutations. After receiving ethics permission in Apr 2015, a total of 20 samples have thus far been collected from HIV-infected subjects (4 co-infected with TB) with high versus low virus load. ISCIII has obtained 40 HIV-1 primary isolates (many from newly diagnosed individuals) and the HIV-1 genetic characterization of these strains performed by near full-length showed a high diversity, including 10 different genetic forms corresponding to 4 subtypes. All 40 isolates are available through the NIBSC repository.
NCAIDS has finished the serum sample screening in the first stage of sampling in China. A total of 1812 samples were amplified and subtyped. Another 50 samples have been collected from HIV infected individuals representing 41 HIV stain isolates. Whole blood samples (90-100ml) were drawn from 50 HIV infected individuals, which were representative of the major circulating subtypes. Currently, there were 44 viruses isolated from 50 samples collected from China as described in the SOP. A total of 1188 samples form 50 HIV-1 infected patients, including 1038 plasma tubes and 44 HIV primary clinics viruses (150 tubes), had been sent to NISBC repository for the production of reference reagents/standards in March, 2017.
KCL has archived after intensive testing and characterization: 65 Latent TB+ HIV-; 40 Pulmonary TB; 17 Extrapulmonary TB; 40 HIV- TB – controls. The total sample available and archived a: 162. All samples are treatment naïve. RNA was Isolated and sequenced from 20 HIV+ plasma samples. The phylogeny and T cell epitope evolution of 79 Mtb strains has been derived through deep sequencing, Through this approach 138 novel T cell epitopes could be and selected peptides were synthesized and tested for immunogenicity.
Nine HIV-1 primary isolates have been obtained by co-culture of PBMCs from patients with stimulated PBMCs from healthy donors. Seven of these 9 (77.8%) HIV-1 primary isolates were obtained from newly diagnosed individuals, including one acute infection, being representative of circulating HIV-1 viruses. Thirteen new HIV-1 functional envelope clones, amplified from plasma RNA from HIV-1-infected individuals, were produced. Sequencing of full-length inserts of these clones was completed and sequences were submitted to GenBank.
In Task 4.2 HIV Peptide pools of 150 peptides each were manufactured for HIV gag and nef. For HBV 157 peptides were synthesised as well as 4 PepMixes for TB (80 vials each were provided for the NIBSC repository. PepMix peptide pools were provided for HIV (2), HBV (1), HCV (2) and M. tuberculosis (2). For HIV 2 peptide microarrays HIV were generated based on a peptide library of 6758 peptides and for HBV a peptide library of 4782 peptides manufactured and printed onto peptide microarrays, Equally 200 slides each with high content libraries for HBV, Mtb, HCV and Plasmodium falciparum.have been generated. Analytical tools and validation protocols for peptide microarray products were developed and tested.
Eight highly pure M. bovis and Mtb proteins (including ESATt6 and CFP10) have been produced by Lionex. MPT64, ACR and HSP65 have now been added. Two single antigen ELISA kits (for the detection of ESAT6 and CFP10) for studying immune responses to the above antigens have been produced. Total of 19 Mtb proteins with relevance to the peptide arrays have been deposited by LUMC. The cDNAs and expression vectors for recombinant production of HIV-1 integrase (INT) and protease (PRT) proteins in mammalian (CHO) cells using QMCF technology have been constructed. LIONEX has made available 16 recombinant antigens of M. tuberculosis, 6 native mycobacterial antigens, and 6 single antigen ELISA kits.
Polymun provided also anti-HIV antibodies: PGT145, and 8 anti-gp41 Abs, 5 anti-gp120 Abs, 2 anti-p24 Abs and 4 gp140 HIV envelope proteins. HCV envelope antigen sE2 and the anti E2 antibody e137 were manufactured for the depository. A complete set of Tb antigens was provided by LUMC. Icosagen has produced and delivered four antibodies against HIV-1 Nef (clones 2F2 and N5) and p24 (clones N17 and N29). In addition, they have produced HIV-1 Tat proteins C-consensus and Bal using E. coli BL21 (DE3) production system. Antibodies and protein were delivered to NIBCS. The development of recombinant antibodies against two Malaria antigens and CyRPA was performed.
In total very well characterize tools for the research in PRD were developed and validated and are now available for the scientific community.
Work Package 5 - Standardisation and Harmonisation of Assays
The main objectives of WP5 are to identify a series of immunological assays for use in vaccine studies across different pathogens, establish an optimised protocol for these assays, and conduct some harmonisation experiments across different laboratories using these optimised protocols. The final objective is to run some clinical samples using these optimised protocols.
The WP has held regular meetings via teleconference, and substantial progress has been made towards our objectives. In the first six months (M0 - M6), the WP collaborators identified and agreed a list of five assays to work on standardising and harmonising, as well as which partners would be involved with each assay. We worked to ensure the latter combined partners experienced with that assay, as well as laboratories new to the procedure, so that technology can be transferred and these specialist laboratory assays can be moved further into the mainstream in Europe. The assays selected provide a balance of pathogen-specific assays that require standardisation, and cross-pathogen assays that need harmonisation and standardisation across platforms. From M7 the Collaborators have been working on standardisation and harmonisation of these assays.
Since the Period 1 (M18) report excellent progress with each of the assays was achieved. For all five assays we have an optimised protocol which was used to conduct some inter-laboratory harmonisation assays. Furthermore, with each of these assays, we planned to run some clinical samples over the remaining 12 months.
Since the Period 2 (M36) report, we have made excellent progress with each of the assays. For all five assays, we have an optimised protocol, which has been used to conduct inter-laboratory harmonisation assays and has been evaluated against pre-existing clinical samples from studies and trials conducted in the partner laboratories.
At the end of this project (M48) we have final Standard Operating Procedures (SOPs) for all of the five assays together with some data on their use with clinical samples. This data will be published in open access, peer-reviewed journals. Furthermore the SOPs are available for anyone to access. The standardisation and harmonisation work conducted in this WP has allowed us to generate robust SOPs which are fit for purpose for the global vaccine community to access and utilise.
Work Package 6 - Access to Biological Reference Reagents and Services
WP6 aims to collect materials from EURIPRED partners and to provide a) free access to biological reference reagents and materials archived at MHRA-NIBSC, b) free access to VFL/ UNIL’s adjuvants and formulation studies, and c) free access to JPTs microarray facility for screening and evaluation. The EURIPRED TNA procedures were developed and the three services were prepared to be available for user projects. All applications received has been reviewed and evaluated by the Users Selection Panel (USP) and decision were made whether to grant access of the requested service or not. MHRA-NIBSC has expanded its repository with new materials from EURIPRED partners and has provided the reagents to the European scientific community through TNA. After the first 5 scheduled calls were announced, limited number of applications was received. An open call was put in place from Dec 2015 to encourage more users to apply and speed up the TNA process.
By M36, a total of 29 users were selected, nine users for accessing microarray facility (2 units), four users for accessing adjuvant and formulation studies (38 units), and 17 users (including one same user also accessing the adjuvant studies) for accessing reagents (226 units). Access to JPT’s microarray facility was provided for screening samples from patients at different stages of tuberculosis. The VFL/UNIL formulation studies allocated during the current reporting period are currently ongoing or to be started. The formulation study allocated during the previous reporting period was successfully completed.
During the last reporting period MHRA NIBSC has expanded its’ repository with new materials from EURIPRED partners and has provided 329 reagents/ units to the European scientific community through TNA. Due to high demand, additional 10 units of access for VFL/UNIL formulation studies were made available for TNA. The open call for applications for TNA was continued and a total of 26 users were selected, 4 user for accessing JPT’s microarray facility (3 units), two users for accessing VFL/UNIL’s adjuvant and formulation studies (10 units), and 22 users for accessing reagents (329 units). All access sessions to JPT’s microarray facility and all VFL/UNIL formulation studies, including those allocated during the previous reporting period, were successfully completed.
Overall, all activities have been completed within the last reporting period with no deviations.
Work Package 7 - Dissemination and Training
EURIPRED website (www.euripred.eu) has been developed for dissemination and advocacy purposes. It has been kept updated on a regular basis. Final changes have been made to ensure it can stay online for the coming 5 years.
Total of thirteen newsletters and 2 flyers have been produced and sent out to approximately 1300 email addresses and made available on the website and to partners for further distribution. A series of meetings took place, and EURIPRED partners were present to network and collaborate, and presented their work. Three web-based and five on-site laboratory trainings were delivered. A number of webinars were prepared and are available online via the EURIPRED website. A series of SOPs and protocols for scientific research were made available online via the EURIPRED website. The project has contributed to the set-up of an Innovative funding instrument INNOVFIN for infectious diseases (including poverty related diseases). EURIPRED partners are involved in the development of the Global TB Vaccine Partnership (GTBVP). The Virtual Institute (VI) platform (http://viprd.eu/) has been developed and structured with various functionalities. Information has been populated on this VI by partners during the project life.
Work Package 8 - Consortium Management
The function of this WP is the management of resources of the whole EURIPRED project, and this WP is responsible for the management and coordination of activities of this project. For the first reporting period, the EURIPRED management team at MHRA successfully established and implemented the management and governance structures and procedures, including the establishment of the Steering Committee, External Advisory Board, Ethics Advisory Committee and the User Selection Panel. During the project life, five consortium assembly meetings were held (Kick off and 4 annual meetings). In conjunction with the 2nd annual meeting held in Nov 2015, the Mid-Term Review meeting was also held in the presence of the EC Project Officer and an external reviewer. In addition, a Stakeholders' meeting on Infrastructure needs for Poverty Related Diseases (PRD) research and three various scientific symposia were also organised with invited external speakers/ experts. The team regularly monitors the project progress by various means, mainly by email, telephone conference calls, discussions in face-to-face meetings, and discussions with the work package leaders (WPLs). The Project Management also collated information from partners and prepared the periodic (M18) and Mid-Term Review (M24) reports. These reports were submitted to the EC in a timely manner.
Since M37 Project Management arranged and held the 3rd and 4th Annual meetings, with all partners and external advisors invited. Each meeting included a social working dinner and separate meetings of the individual advisory boards as well as the Steering Committee. The decision to hold the 4th Annual meeting before the end of the project was taken by the Steering Committee at their meeting at the 3rd Annual Meeting. It was felt that the 4th Annual Meeting (final meeting) would be better held at M40 rather than at the end of the project, as this would provide an opportunity to identify any last minute problems and allow some time to resolve these to ensure that deliverables would be met by the end of the project. The final meeting was held in London on Jun 2017 and focussed heavily on ensuring that all project work would complete before the end of the project in October 2017. Discussions were held at the 4th Annual Meeting, led by partner 2 (KCL India) on the use of the sequence data gathered epidemiological data for publication. This was taken forward by the biobank partners.
For the last reporting period, the EURIPRED Project Management has coordinated the submission of the M36 reporting, both scientific and financial reports on behalf of the project partners. The partner budgets were distributed following receipt of the interim payment and budget re-allocation was managed between two partners due to underspend. Final project reports for M48 were compiled leading up the end of the project and immediately following the close of the project, consisting of scientific and financial reports, an ethics report and a final report of the whole EURIPRED project for submission to the EC by 30th December 2017. Project Management ensured that all partners receiving in excess of 375k Euro from the EC contributions conducted an audit to produce a Certificate on Financial Statement and provided management support to all partners for the complete reporting process. We also submitted all deliverable reports collected from partners into the EC portal. In addition, two amendments of the Grant Agreement have been submitted to and accepted by the EC.
Potential Impact:
The consortium is supported by a strong collaboration between the partners with the overall goal of enhancing user access to world-level research infrastructures. New products such as clinical isolates representative of HIV, hepatitis virus, Mycobacterium tuberculosis and Plasmodium falciparum strains circulating within Europe, China, India, Russia and Africa serve as important sources for interdisciplinary research, and thus contribute directly to scientific European excellence in a competitive research and economic domain. The partners involved in patients’ samples collection and basic R&D are placed to provide unique access to a wide range of materials, that will drive both clinical and preclinical development of vaccines as well as underpin and strengthen basic research on infection, immunology and pathways to new interventions. Proteins, peptides, and complex compounds, such as defined glycolipids, are critical to undertaking fundamental research in these important infectious diseases. Wider access to such materials to the European scientific community provide a much strengthened reagent and materials infrastructure that allow novel and cross-linking strategies to be developed.
The networking activities described in EURIPRED exploit the state-of-the-art expertise and know-how on recombinant protein production, antibody production, microarray technology, facilities, and assay harmonisation. Essential inter-laboratory interactions and a culture of cooperation and integration were implemented through collaborative study processes used to validate reference reagents. EURIPRED has facilitated links between partners working on TB and malaria assay harmonisation. These joint research activities between laboratories promote data sharing and collaborations which in turn drive the project forward and ensure impact. The development of a Virtual Institute containing various functionalities and up-to-date scientific information on the specific disease areas promote e-learning and enable full exploitation of expertise present within the consortium.
The EURIPRED TNA services provided useful resources free of charge to European scientists to facilitate their research activities. All the biological materials and reference reagents generated during the project life are stored and will be made available to wider scientific communities upon requests. These reagents will be distributed by the NIBSC CFAR repository. A full detail of EURIPRED TNA impact report is attached.
List of Websites:
The website address of the EURIPRED project is http://www.euripred.eu/ which will be available for 5 years following the completion of the project.
EURIPRED is a collaborative infrastructure FP7 project coordinated by the Project Management Team at MHRA NIBSC. During the last four years of operations, EURIPRED has demonstrated the feasibility of integrating international resources into a single specialised infrastructure to support European HIV, TB, malaria and hepatitis B/ C virus studies from early drug, vaccine and microbicide discovery to clinical trials. The project achieved its goals by creating partnerships between European scientists and international research teams from disease endemic countries and strong collaborations between industry and public sector research. This has brought international resources and facilities together to develop cost-effective products/ reagents for the European scientists. EURIPRED has successfully integrated worldwide resources to allow European access to shared biological materials and research reagents.
EURIPRED aims to develop, characterise and make available a selection of reference reagents/ standards for access through Transnational access (TNA). This has been achieved by partners from various research institutes and biotechnology companies working together. The six Biobanks within the EURIPRED project have collected more than 1000 new clinical samples from selected patients from six different countries including the Kenya, Russia, China, India, Spain and UK. These biological materials are well characterised and some of them have been used to generate novel research and reference reagents. About 300 new research and reference reagents have been produced, characterised and made available through TNA during the project life. Most of the materials have been deposited at the NIBSC Centre for AIDS Reagents Repository (CFAR) where they will be held securely under the ISO9001 quality system and made available to researchers under Material Transfer Agreements.
One important measure of success of the project is the provision of materials and services to researchers through the EURIPRED TNA process. Free access to all EURIPRED services have been provided to 41 scientific research projects across various infectious disease areas including HIV, tuberculosis, malaria, hepatitis and emerging viral infections. The end user applications were selected through a scientific evaluation process conducted by a group of experts in the relevant areas based on scientific excellence, feasibility and impact.
Joint research activities have been focussed on the assay harmonisation of a series of immunological assays used in vaccine studies across different pathogens. Some clinical samples were used to optimise the final harmonised protocols and final Standard Operating Procedures (SOPs) of assays were prepared and made available on the EURIPRED website for wider access to the scientific community. The process of harmonisation and data obtained will be published in open access, peer-reviewed journals.
EURIPRED provided three web-based and five on-site laboratory trainings. A number of webinars and a series of SOPs and protocols for scientific research are available online via the EURIPRED website. The Virtual Institute platform (http://viprd.eu/) has been developed and structured with various functionalities. Information has been populated on this Virtual Institute by partners during the project life.
Project Context and Objectives:
HIV/AIDS, Tuberculosis (TB) and Malaria alone account for more than six million deaths worldwide every year. Despite substantial efforts made in recent years, Poverty Related Diseases (PRDs) are still spreading. New therapeutic interventions are therefore urgently required to combat PRDs. The existence of a well-developed HIV/ TB/ malaria infrastructure presents a prime opportunity to address other sexually transmitted diseases such as viral hepatitis efficiently and effectively. The overall goal of the EURIPRED is to coordinate and integrate international resources into a single specialised infrastructure to support European HIV, TB, malaria and hepatitis B/ C virus studies from early drug, vaccine and microbicide discovery to clinical trials. This will be achieved by creating partnerships between European scientists and international research teams from disease endemic countries and strong collaborations between industry and public sector research. Although vaccines, drugs and microbicide research activities are being conducted in the European Union (EU), there is no single European infrastructure that brings international resources and facilities together to develop cost-effective products/ reagents for the European market. To underpin this need, EURIPRED will integrate worldwide resources to allow European access to shared reagents. This integrated approach will strengthen international cooperation, increase research capacity in EU and developing countries and significantly contribute to the European Research Area (ERA). By minimising fragmentation and duplication of research efforts and pooling fragmented resources EURIPRED can improve European research efficiency and effectiveness.
Delivery of these goals will be achieved through the following scientific and technical objectives:
1) Strengthen, broaden and exchange knowledge and know-how between partners
2) Promote and enable communication with other stakeholders and projects by networking
3) Provide the scientific community with transnational access to participant-owned European and international resource infrastructures
4) Horizontally collaborate with infrastructures and services within the consortium
The consortium is supported by a strong collaboration between the partners with the overall goal of enhancing user access to world-level research infrastructures, thanks to their complementarities. New products such as clinical isolates representative of HIV, Hepatitis B and C virus, M. tuberculosis and
Plasmodium falciparum strains circulating within Europe, China, India, Russia and Africa will serve as important sources for interdisciplinary research, and thus contribute directly to scientific European excellence in a competitive research and economic domain. The partners involved in clinical studies of TB, vaccine clinical trials and basic R&D are placed to provide unique access to a wide range of materials, that will drive both clinical and preclinical development of vaccines as well as underpin and strengthen basic research on infection, immunology and pathways to new interventions. Proteins, peptides, and complex compounds such as defined glycolipids are critical to undertaking fundamental research in this important infectious disease. Wider access to such materials to the European scientific community will provide a much strengthened reagent and materials infrastructure that will allow novel and cross-linking strategies to be developed
The project consists of three main streams of activities including networking activities (WP1, 2 & 7), joint research activities (WP3, 4 & 5) and transnational access (WP6). The project management is performed in WP8.
Project Results:
Work Package 1 - Resource Management and Quality Assurance
One main goal of EURIPRED is the collection of new specimens of HIV, TB, Malaria and viral hepatitis through the collaboration of various biobanks worldwide. The partners involved in WP1 brings together an extensive range of technical platforms, protocols, know-how and pooled expertise on quality assurance, database set-up and management and biobanking of clinical and research materials. This resource provides guidance, expert knowledge on reagent and data acquisition, quality control testing, storage and international specimen transport. Furthermore the biobanks have worked together to harmonise and standardise processes for reagent management, testing and transport. KCL circulated up-to-date standard operating procedures (SOPs) describing the process of sample collection, storage and blood fractionation. In addition, an Ethics Advisory Committee (EAC) has been created and overviewed the ethical aspects of the project. In order to ensure quality assurance during the distribution of reference reagents/ standards developed by WP4, NIBSC-CFAR has renewed the accreditation to ISO9001:2008 for receipt, storage and distribution of reagents. The collection and analysis of clinical samples generate a large amount of data. In order to centralise this information, UNICUM has developed the IT structure of the Virtual Institute for Poverty Related Diseases (VIPRD). The VIPRD is a web-based platform aiming at gathering and making available a central biobanks registrar for the EURIPRED project, as well as promoting scientific interactions through network functionality.
During last period of the project, all deliverables have been completed. In addition, the ongoing harmonization of biobanking activities has continued. We have a well-managed and accessible reagents and clinical materials available to the broader scientific community thereby fulfilling the legacy aspects of the EURIPRED project.
Work Package 2 - Networking with other Groups and Projects
The overall goal of WP2 is to network with international research programmes and projects to establish a wider network that will allow integration of HIV, Hepatitis, TB and Malaria research within Europe and beyond and promote the EURIPRED project. During the first reporting period was to perform an inventory of already existing initiatives and research activity in the field of poverty related diseases (HIV, HBV, HCV, TB and malaria). The WP2 partners generated a survey to be filled in by all EURIPRED researchers aiming at collecting information on collaboration/ network among EURIPRED partners in the form of a catalogue. Such overview was disseminated to all partners to foster interactions among the EURIPRED partners and beyond. Analysis of the respondent answers helps identifying gaps and needs for joint research activities and potential for new collaborations. The output has been combined into a strategic agenda. Ultimately the networking activities undertaken will improve and globalize research culture leading to a more interdisciplinary approach and solution to scientific questions.
During the second period, we aimed at pursuing the effort to bring awareness on the EURIPRED project and TNA opportunities together with integrating the Virtual Institute (VI) under development in the networking strategy. In addition to the pre-existing links and networks via the project partners, the partners aimed at consolidating the resources available via the catalogue already produced. Special attention was given in identifying gaps in the catalogue and missing key stakeholders/ initiatives in the poverty related diseases (charities, foundations, etc). An effort was made in identifying the key persons to be approached to initiate communication and foster visibility of the project and bring awareness. In addition, the final architecture of Intranet/ Extranet platforms of the VI was built. All developed functionalities were tested, installed and used in WP2 for strengthening communication within the partners and with external networks and projects. Access to the extranet has been provided to 42 external institutions (MS 13 new collaboration set-up) and special attention has been given by MHRA to foster new collaborations (visit Pasteur Institute in Shanghai, 24 October 2016). A strategic agenda was developed to provide an integrated overview of the activities to be performed within the WP2 networking.
The last period of the project aimed at ensuring the visibility of EURIPRED and to give a final push towards utilisation of the TNA offerings remaining on the project. In the meantime, the fine tuning of the VI functionalities was undertaken for further integration of the VI into the networking strategy. A final update of the catalogue was undertaken to reflect the new networking opportunities that came from newly funded projects (D2.4). A special effort was made in reaching out to all identified organisations, charities and project coordinators listed in the catalogue to ensure the visibility of the project.
Work Package 3 - Patient recruitment, Sample selection and Characterisation of Biological Materials
The objective of WP3 is to establish a comprehensive biobank of HIV, HBV, HCV, malaria and M.tb for trans-national access from the unique population and to provide the biological materials for the development of novel reagents. The patient recruitment, sample selection and characterization of biological materials are the key process for ensuring the smooth implementation of the project. This work package aims to the collection and characterization of pathogens from multiple sites and has been expanded the collection by assembling new cohorts to capture contemporary circulating strains of HIV, HBV, HCV, malaria and M.tb from the UK, India, China, Russia, Spain and Kenya, characterize the genetic and biological characteristics, and then supply biological materials for primary use in the EURIPRED project.
From the beginning of the project, KCL-UK has collected 356 HIV+ samples, KCL-India 74 HIV+ and 122 TB+ samples; NCAIDS 50 HIV+ samples; Gamaleya 70 HIV+, 39 HIV-Mtb and 77 HIV-HCV+ samples; KEMRI 100 HIV-Mtb and 28 HIV-Malaria samples; ISCIII 90 HIV+ samples. As the timing of work packages, biological and epidemiological properties of the newly and previously collected samples from all sites were characterized by the collection institutes including viral load, CD4 counts, pol gene, the neutralizing activities and so on. A total of 76 HIV-1 viruses were isolated, 31 viruses from Chinese patients and 5 isolates from Russian patients and 40 from Spanish patients. Full length genomic sequences, specific features, co-receptor usage and phylogenetic analyses of new and previous HIV-1 isolates were analysed. HIV whole genome of plasma samples from India and 79 Mtb whole genomes were identified by KCL-India. A PCR to initiate sequencing of the Gag region of HIV was established by KCL-UK, which had obtained the cohort 70 sequences. In addition, MHRA-NIBSC had set up a protocol to identify the sequence of HIV by RT-PCR +NGS, and had performed it on EURIPRED samples collected. Library design PepMix pools were finished for 3 Antigens (2 HIV - gag & nef and 1 HBV - C-protein), and library design Peptide Microarrays were finished for 2 Array-Libraries (HIV & HBV) by JPT.
For the period M37-M48, the patient recruitments were replenished with 121 Russian patients with 21 HIV/HCV co-infections and 63 HIV/TB co-infections, 18 Spanish HIV patients infected with viruses of subtype B, non-B subtypes and circulating recombinant forms (CRFs). The samples and the patient characteristics were collected, and the collected samples were characterized by collection institutes including viral load, CD4 counts, the neutralizing activities, and so on. As the timing of work packages, the dominant or novel viruses were isolated from the samples collected from China, Russia and Spain, of which the HIV-1 near full-length genome was amplified and sequenced. The co-receptor usage of novel/dominant HIV-1 isolates was also determined by the collection sites. All the samples including the plasma/serum samples, HIV-1 primary isolates and PBMCs, had been sent to NIBSC repository from the multiple sites of WP3, 110 HIV positive samples from Gamaleya, 130 HIV samples from ISCIII, 50 HIV positive samples (1038 tubes for plasma) and 44 HIV clinical isolates(150 tubs) from China, respectively. Gamaleya evaluated the anti-HIV activity of anti-MTB drugs in Russian patients and discovered two anti-TB drugs (Linezolid and Isoniazid) showed dual inhibitory effect against the two infections (TB and HIV). In addition to the libraries for peptide microarrays towards the pathogens HIV, HCV, HBV and M.tb the library for Plasmodium falciparum and P. vivax and an additional HIV library for sequence information gathered in the EURIPRED project were designed by JPT. To support the WP3 task 3.2 on sample characterisation of samples, MHRA-NIBSC amplified 30 HIV envelope genes from clinical samples collected through EURIPRED with various genetic background including subtypes B, C, F, G, CRF01_AE, CRF02AG, CRF03_AB, CRF05_D/F, CRF07_BC, CRF08_BC, CRF35_AD and CRF43_02G, clones it and tested their functionality.
Work Package 4 - Development and Evaluation of Reference Reagents
WP4 aims to develop, characterise, and make available a selection of reference reagents/ standards for access through Transnational Access (TNA). Reference reagents developed through this platform will be tested for functionality, and protocols and final reference reagents specifications will be shared. In the first six months, the WP partners identified and agreed on the selection criteria for biological materials for development of reference reagents (Task 4.1) as well as for the priorities for the development of reference reagents/standards (Task 4.2).
During the period until month 48 KCL-India has sequenced and characterised 19 extensive drug resistant Mtb strains for mutations in known T cell epitopes. In total 79 Mtb whole genomes have been scanned for mutations in CD4 T-cell epitopes. The screen of 1101 T cell epitopes revealed 138 new mutations. After receiving ethics permission in Apr 2015, a total of 20 samples have thus far been collected from HIV-infected subjects (4 co-infected with TB) with high versus low virus load. ISCIII has obtained 40 HIV-1 primary isolates (many from newly diagnosed individuals) and the HIV-1 genetic characterization of these strains performed by near full-length showed a high diversity, including 10 different genetic forms corresponding to 4 subtypes. All 40 isolates are available through the NIBSC repository.
NCAIDS has finished the serum sample screening in the first stage of sampling in China. A total of 1812 samples were amplified and subtyped. Another 50 samples have been collected from HIV infected individuals representing 41 HIV stain isolates. Whole blood samples (90-100ml) were drawn from 50 HIV infected individuals, which were representative of the major circulating subtypes. Currently, there were 44 viruses isolated from 50 samples collected from China as described in the SOP. A total of 1188 samples form 50 HIV-1 infected patients, including 1038 plasma tubes and 44 HIV primary clinics viruses (150 tubes), had been sent to NISBC repository for the production of reference reagents/standards in March, 2017.
KCL has archived after intensive testing and characterization: 65 Latent TB+ HIV-; 40 Pulmonary TB; 17 Extrapulmonary TB; 40 HIV- TB – controls. The total sample available and archived a: 162. All samples are treatment naïve. RNA was Isolated and sequenced from 20 HIV+ plasma samples. The phylogeny and T cell epitope evolution of 79 Mtb strains has been derived through deep sequencing, Through this approach 138 novel T cell epitopes could be and selected peptides were synthesized and tested for immunogenicity.
Nine HIV-1 primary isolates have been obtained by co-culture of PBMCs from patients with stimulated PBMCs from healthy donors. Seven of these 9 (77.8%) HIV-1 primary isolates were obtained from newly diagnosed individuals, including one acute infection, being representative of circulating HIV-1 viruses. Thirteen new HIV-1 functional envelope clones, amplified from plasma RNA from HIV-1-infected individuals, were produced. Sequencing of full-length inserts of these clones was completed and sequences were submitted to GenBank.
In Task 4.2 HIV Peptide pools of 150 peptides each were manufactured for HIV gag and nef. For HBV 157 peptides were synthesised as well as 4 PepMixes for TB (80 vials each were provided for the NIBSC repository. PepMix peptide pools were provided for HIV (2), HBV (1), HCV (2) and M. tuberculosis (2). For HIV 2 peptide microarrays HIV were generated based on a peptide library of 6758 peptides and for HBV a peptide library of 4782 peptides manufactured and printed onto peptide microarrays, Equally 200 slides each with high content libraries for HBV, Mtb, HCV and Plasmodium falciparum.have been generated. Analytical tools and validation protocols for peptide microarray products were developed and tested.
Eight highly pure M. bovis and Mtb proteins (including ESATt6 and CFP10) have been produced by Lionex. MPT64, ACR and HSP65 have now been added. Two single antigen ELISA kits (for the detection of ESAT6 and CFP10) for studying immune responses to the above antigens have been produced. Total of 19 Mtb proteins with relevance to the peptide arrays have been deposited by LUMC. The cDNAs and expression vectors for recombinant production of HIV-1 integrase (INT) and protease (PRT) proteins in mammalian (CHO) cells using QMCF technology have been constructed. LIONEX has made available 16 recombinant antigens of M. tuberculosis, 6 native mycobacterial antigens, and 6 single antigen ELISA kits.
Polymun provided also anti-HIV antibodies: PGT145, and 8 anti-gp41 Abs, 5 anti-gp120 Abs, 2 anti-p24 Abs and 4 gp140 HIV envelope proteins. HCV envelope antigen sE2 and the anti E2 antibody e137 were manufactured for the depository. A complete set of Tb antigens was provided by LUMC. Icosagen has produced and delivered four antibodies against HIV-1 Nef (clones 2F2 and N5) and p24 (clones N17 and N29). In addition, they have produced HIV-1 Tat proteins C-consensus and Bal using E. coli BL21 (DE3) production system. Antibodies and protein were delivered to NIBCS. The development of recombinant antibodies against two Malaria antigens and CyRPA was performed.
In total very well characterize tools for the research in PRD were developed and validated and are now available for the scientific community.
Work Package 5 - Standardisation and Harmonisation of Assays
The main objectives of WP5 are to identify a series of immunological assays for use in vaccine studies across different pathogens, establish an optimised protocol for these assays, and conduct some harmonisation experiments across different laboratories using these optimised protocols. The final objective is to run some clinical samples using these optimised protocols.
The WP has held regular meetings via teleconference, and substantial progress has been made towards our objectives. In the first six months (M0 - M6), the WP collaborators identified and agreed a list of five assays to work on standardising and harmonising, as well as which partners would be involved with each assay. We worked to ensure the latter combined partners experienced with that assay, as well as laboratories new to the procedure, so that technology can be transferred and these specialist laboratory assays can be moved further into the mainstream in Europe. The assays selected provide a balance of pathogen-specific assays that require standardisation, and cross-pathogen assays that need harmonisation and standardisation across platforms. From M7 the Collaborators have been working on standardisation and harmonisation of these assays.
Since the Period 1 (M18) report excellent progress with each of the assays was achieved. For all five assays we have an optimised protocol which was used to conduct some inter-laboratory harmonisation assays. Furthermore, with each of these assays, we planned to run some clinical samples over the remaining 12 months.
Since the Period 2 (M36) report, we have made excellent progress with each of the assays. For all five assays, we have an optimised protocol, which has been used to conduct inter-laboratory harmonisation assays and has been evaluated against pre-existing clinical samples from studies and trials conducted in the partner laboratories.
At the end of this project (M48) we have final Standard Operating Procedures (SOPs) for all of the five assays together with some data on their use with clinical samples. This data will be published in open access, peer-reviewed journals. Furthermore the SOPs are available for anyone to access. The standardisation and harmonisation work conducted in this WP has allowed us to generate robust SOPs which are fit for purpose for the global vaccine community to access and utilise.
Work Package 6 - Access to Biological Reference Reagents and Services
WP6 aims to collect materials from EURIPRED partners and to provide a) free access to biological reference reagents and materials archived at MHRA-NIBSC, b) free access to VFL/ UNIL’s adjuvants and formulation studies, and c) free access to JPTs microarray facility for screening and evaluation. The EURIPRED TNA procedures were developed and the three services were prepared to be available for user projects. All applications received has been reviewed and evaluated by the Users Selection Panel (USP) and decision were made whether to grant access of the requested service or not. MHRA-NIBSC has expanded its repository with new materials from EURIPRED partners and has provided the reagents to the European scientific community through TNA. After the first 5 scheduled calls were announced, limited number of applications was received. An open call was put in place from Dec 2015 to encourage more users to apply and speed up the TNA process.
By M36, a total of 29 users were selected, nine users for accessing microarray facility (2 units), four users for accessing adjuvant and formulation studies (38 units), and 17 users (including one same user also accessing the adjuvant studies) for accessing reagents (226 units). Access to JPT’s microarray facility was provided for screening samples from patients at different stages of tuberculosis. The VFL/UNIL formulation studies allocated during the current reporting period are currently ongoing or to be started. The formulation study allocated during the previous reporting period was successfully completed.
During the last reporting period MHRA NIBSC has expanded its’ repository with new materials from EURIPRED partners and has provided 329 reagents/ units to the European scientific community through TNA. Due to high demand, additional 10 units of access for VFL/UNIL formulation studies were made available for TNA. The open call for applications for TNA was continued and a total of 26 users were selected, 4 user for accessing JPT’s microarray facility (3 units), two users for accessing VFL/UNIL’s adjuvant and formulation studies (10 units), and 22 users for accessing reagents (329 units). All access sessions to JPT’s microarray facility and all VFL/UNIL formulation studies, including those allocated during the previous reporting period, were successfully completed.
Overall, all activities have been completed within the last reporting period with no deviations.
Work Package 7 - Dissemination and Training
EURIPRED website (www.euripred.eu) has been developed for dissemination and advocacy purposes. It has been kept updated on a regular basis. Final changes have been made to ensure it can stay online for the coming 5 years.
Total of thirteen newsletters and 2 flyers have been produced and sent out to approximately 1300 email addresses and made available on the website and to partners for further distribution. A series of meetings took place, and EURIPRED partners were present to network and collaborate, and presented their work. Three web-based and five on-site laboratory trainings were delivered. A number of webinars were prepared and are available online via the EURIPRED website. A series of SOPs and protocols for scientific research were made available online via the EURIPRED website. The project has contributed to the set-up of an Innovative funding instrument INNOVFIN for infectious diseases (including poverty related diseases). EURIPRED partners are involved in the development of the Global TB Vaccine Partnership (GTBVP). The Virtual Institute (VI) platform (http://viprd.eu/) has been developed and structured with various functionalities. Information has been populated on this VI by partners during the project life.
Work Package 8 - Consortium Management
The function of this WP is the management of resources of the whole EURIPRED project, and this WP is responsible for the management and coordination of activities of this project. For the first reporting period, the EURIPRED management team at MHRA successfully established and implemented the management and governance structures and procedures, including the establishment of the Steering Committee, External Advisory Board, Ethics Advisory Committee and the User Selection Panel. During the project life, five consortium assembly meetings were held (Kick off and 4 annual meetings). In conjunction with the 2nd annual meeting held in Nov 2015, the Mid-Term Review meeting was also held in the presence of the EC Project Officer and an external reviewer. In addition, a Stakeholders' meeting on Infrastructure needs for Poverty Related Diseases (PRD) research and three various scientific symposia were also organised with invited external speakers/ experts. The team regularly monitors the project progress by various means, mainly by email, telephone conference calls, discussions in face-to-face meetings, and discussions with the work package leaders (WPLs). The Project Management also collated information from partners and prepared the periodic (M18) and Mid-Term Review (M24) reports. These reports were submitted to the EC in a timely manner.
Since M37 Project Management arranged and held the 3rd and 4th Annual meetings, with all partners and external advisors invited. Each meeting included a social working dinner and separate meetings of the individual advisory boards as well as the Steering Committee. The decision to hold the 4th Annual meeting before the end of the project was taken by the Steering Committee at their meeting at the 3rd Annual Meeting. It was felt that the 4th Annual Meeting (final meeting) would be better held at M40 rather than at the end of the project, as this would provide an opportunity to identify any last minute problems and allow some time to resolve these to ensure that deliverables would be met by the end of the project. The final meeting was held in London on Jun 2017 and focussed heavily on ensuring that all project work would complete before the end of the project in October 2017. Discussions were held at the 4th Annual Meeting, led by partner 2 (KCL India) on the use of the sequence data gathered epidemiological data for publication. This was taken forward by the biobank partners.
For the last reporting period, the EURIPRED Project Management has coordinated the submission of the M36 reporting, both scientific and financial reports on behalf of the project partners. The partner budgets were distributed following receipt of the interim payment and budget re-allocation was managed between two partners due to underspend. Final project reports for M48 were compiled leading up the end of the project and immediately following the close of the project, consisting of scientific and financial reports, an ethics report and a final report of the whole EURIPRED project for submission to the EC by 30th December 2017. Project Management ensured that all partners receiving in excess of 375k Euro from the EC contributions conducted an audit to produce a Certificate on Financial Statement and provided management support to all partners for the complete reporting process. We also submitted all deliverable reports collected from partners into the EC portal. In addition, two amendments of the Grant Agreement have been submitted to and accepted by the EC.
Potential Impact:
The consortium is supported by a strong collaboration between the partners with the overall goal of enhancing user access to world-level research infrastructures. New products such as clinical isolates representative of HIV, hepatitis virus, Mycobacterium tuberculosis and Plasmodium falciparum strains circulating within Europe, China, India, Russia and Africa serve as important sources for interdisciplinary research, and thus contribute directly to scientific European excellence in a competitive research and economic domain. The partners involved in patients’ samples collection and basic R&D are placed to provide unique access to a wide range of materials, that will drive both clinical and preclinical development of vaccines as well as underpin and strengthen basic research on infection, immunology and pathways to new interventions. Proteins, peptides, and complex compounds, such as defined glycolipids, are critical to undertaking fundamental research in these important infectious diseases. Wider access to such materials to the European scientific community provide a much strengthened reagent and materials infrastructure that allow novel and cross-linking strategies to be developed.
The networking activities described in EURIPRED exploit the state-of-the-art expertise and know-how on recombinant protein production, antibody production, microarray technology, facilities, and assay harmonisation. Essential inter-laboratory interactions and a culture of cooperation and integration were implemented through collaborative study processes used to validate reference reagents. EURIPRED has facilitated links between partners working on TB and malaria assay harmonisation. These joint research activities between laboratories promote data sharing and collaborations which in turn drive the project forward and ensure impact. The development of a Virtual Institute containing various functionalities and up-to-date scientific information on the specific disease areas promote e-learning and enable full exploitation of expertise present within the consortium.
The EURIPRED TNA services provided useful resources free of charge to European scientists to facilitate their research activities. All the biological materials and reference reagents generated during the project life are stored and will be made available to wider scientific communities upon requests. These reagents will be distributed by the NIBSC CFAR repository. A full detail of EURIPRED TNA impact report is attached.
List of Websites:
The website address of the EURIPRED project is http://www.euripred.eu/ which will be available for 5 years following the completion of the project.
