Community Research and Development Information Service - CORDIS

FP7

EURIPRED Report Summary

Project ID: 312661
Funded under: FP7-INFRASTRUCTURES
Country: United Kingdom

Periodic Report Summary 2 - EURIPRED (European Research Infrastructures for Poverty Related Diseases)

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 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.

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 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 Virtual Institute 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.

Work Package 3 - Patient recruitment, Sample selection and Characterisation of Biological Materials
The patient recruitment, sample selection and characterization of biological materials are the key process for ensuring the smooth implementation of the project. WP3 aims to the collection and characterization of pathogens from multiple sites: other labour-intensive tasks intimately associated with these activities (e.g. development of SOPs, management of samples, data transfer, ethics and legal considerations) form part of WP1. The objective of WP3 is to expand these collections by assembling new cohorts to capture contemporary circulating strains of HIV, M. tuberculosis (Mtb), HCV, characterize the genetic and biological characteristics, then supply these biological materials for TransNational Access (TNA) from the project. The sample collection and characterization are mostly on schedule.
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.

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 36 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 were drawn from each HIV infected individual.
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. The synthesis of 2 HCV PepMixes was started. For HIV 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 and HCV have been generated. The library for plasmodium species is under development. Eight highly pure M. bovis and Mtb proteins (including ESATt6 and CFP10) have been produced. Also 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. 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. Manufacturing of the HCV envelope antigen sE2 is ongoing and the anti E2 antibody e137 for the depository. 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. Current work includes development of recombinant antibodies against two Malaria antigens and CyRPA.

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, 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 month seven the Collaborators have been working on standardisation and harmonisation of these assays.
Since the M18 report we have made excellent progress with each of the assays. For all 5 assays we have an optimised protocol which is now being used to conduct some inter-laboratory harmonisation assays. Furthermore, with each of these assays, we plan to run some clinical samples over the remaining 12 months.
At the end of this project we will have final Standard Operating Procedures for all of the 5 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 will be available for anyone to access. The standardisation and harmonisation work conducted in this workpackage 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 will be reviewed and evaluated by the Users Selection Panel (USP) and decision will be 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.
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. Overall, all activities will be continued until the end of the EURIPRED project with no deviations foreseen.

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. Total of thirteen newsletters and 2 flyers have been produced and sent out to approximately 1300 email addresses and made available on the website. 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 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 with various functionalities. Information is currently putting on this VI by partners.

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. To date, four consortium assembly meetings were held (Kick off and 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.

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 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 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 will provide a much strengthened reagent and materials infrastructure that will 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 will be implemented through collaborative study processes used to validate reference reagents. Furthermore, joint research activities between laboratories will promote data sharing and collaborations which in turn will drive the project forward and ensure impact. The development of a virtual institute containing up-to-date scientific information on the specific disease areas will promote e-learning and enable full exploitation of expertise present within the consortium.

List of Websites:
http://www.euripred.eu/

Contact

Amanda King, (Business Development Manager)
Tel.: +44 1707 641352
Fax: +44 1707 641060
E-mail
Record Number: 197864 / Last updated on: 2017-05-16