About TRANSVAC

Background

Vaccines are one of the most successful and cost-effective public health tools for disease prevention. However, their development is time-consuming and complex, requiring a combination of specialised skills and technical capacities not readily available at a single organisation. In order to facilitate access to these skills and capacities, and to promote collaborations in the European vaccine landscape - aiming thereby to accelerate the development of safe, effective and affordable vaccines - the EC, in the context of the Horizon 2020 Framework Programme, has recently funded “TRANSVAC2”, a European vaccine research and development (R&D) infrastructure.

TRANSVAC2 builds upon the success of TRANSVAC, the European Network of Vaccine Research and Development funded under the EC´s previous Framework Programme (FP7). TRANSVAC made significant contributions to the European vaccine development landscape, providing scientific-technical services to more than 29 vaccine projects and developing a roadmap for the establishment of a sustainable European vaccine R&D.

Objectives

TRANSVAC supports innovation for both prophylactic and therapeutic vaccine development. High quality technical services across four different service platforms are offered: Technology (for process development and GMP production), Immunocorrelates & Systems Biology, Animal models, and support for Clinical Trials. Academic and non-academic research groups, including SMEs, can apply to benefit from the expertise, reagents, and facilities offered by TRANSVAC2 to accelerate the development of their vaccines. The next call for applications will be launched on this website on 15 October 2017.

TRANSVAC will further accelerate vaccine development by developing and applying cutting-edge technologies to address critical issues in modern vaccine development and thereby increase the quality of services provided. In addition, TRANSVAC will continue to establish a sustainable vaccine development infrastructure in Europe.

TRANSVAC also offers training courses to provide fundamental and advanced knowledge on a wide-range of vaccine development-related topics. Training modules will be harmonised with existing European vaccinology courses, aiming to complement existing infrastructures and activities. TRANSVAC will therefore centralise and expand the training opportunities available to the European vaccine community.

With this comprehensive approach, TRANSVAC2 functions as a leverage and innovation catalyst between all stakeholders involved in vaccine R&D in Europe, and contributes to the development of effective products to address European and global health challenges. This reinforces the European leadership in controlling the burden and spread of diseases, and the economic assets represented by vaccine developers in Europe.

Organisational structure

The TRANSVAC2 organisational structure includes three types of consortium bodies: strategic bodies, implementation bodies and advisory bodies.

Strategic bodies:

  • General Assembly
  • Steering Committee

Implementation bodies:

  • Coordinator
  • Project Management Team
  • Platform Leaders/Co-leaders
  • Work Package Leaders

Advisory bodies:

  • Scientific and Ethics Advisory Committee
  • Independent Ethical Advisor
  • Board of Stakeholders
  • User Selection Panel

The diagram below shows the overall organisational structure of TRANSVAC2, which also shows besides the four service platforms and the linked joint research activities (JRA), the network activities.

Organisational structure of TRANSVAC2: (NA: Networking Activities; JRA: Joint Research Activities; TNA: Transnational Access Activities)

Organisational structure of TRANSVAC2

Research activities

TRANSVAC’s joint research activities (JRAs) aim to address current major gaps in vaccine development knowledge and are designed to feed directly into and to support the TNA activities. The TRANSVAC research activities focus heavily on improving predictive assays, adjuvants, animal models, and systems biology. As the lack of a credible and validated animal model is reality for the majority of diseases, this represents a major roadblock in rapidly and reliably advancing vaccine candidates through the pipeline. In parallel, several animal models currently exist that are presumed to be credible predictors of vaccine efficacy in humans, but which have only very limited correlation with human protection, and which are used simply because no other alternatives exist. Research will aim to improve the predictive value of animal models for vaccine evaluation, provide consultancy on the selection of appropriate models, and develop innovative approaches to characterise in vivo antigen behaviour and host responses whilst reducing animal use. Systems biology research will aim to identify and validate mathematical models that can accurately predict interactions between immune system components in relation to vaccination, as well as develop state-of-the-art methods for the structural and functional analysis of vaccine candidates. In addition, the systems biology research will heavily support the activities to improve the predictability of animal models. The rational use of adjuvants will be studied in detail, as very often researchers use a “shotgun” approach with adjuvants, testing entire panels with their antigens in the search for improved immune responses. Therefore adjuvant research activities will aim to develop stable formulations (and combinations thereof) for the focused and rational improvement of specific aspects of the immune response, as required in light of the unformulated antigen’s in vivo immunoprofile. Predictive assay research will aim to develop assays that are of validated and reproducible benefit to vaccine development. This will be underpinned and supported by systems biology research, leading to the improvement of predictability of assays.

Regulatory support

Regional, national, and European regulators play a critical role in guaranteeing vaccine quality, and act as facilitators by providing scientific advice to vaccine researchers. It is therefore essential that “regulatory science” is part of the process of innovation, in order to fulfil its role in the assessment of new technologies and new concepts. The regulatory activities in TRANSVAC will address two goals: (i) to offer advice to scientists, and (ii) to stimulate business intelligence, thus identifying scientific areas that should be recommended for further development, ensuring that regulators can gain access to the data needed for them to make rational and science-based decisions. In order to achieve the first goal, the regulatory work package will offer user-friendly access to a database compiling current information on the regulatory and ethical requirements for clinical trials and for marketing authorisation related to prophylactic and therapeutic vaccines. The second objective will be to provide customised advice to the other work packages in the consortium, to users through specific consultancy agreements, and to regulators through policy change proposals. The regulatory work package will provide consensus science-based suggestions for the adaptation of regulatory requirements. The second goal will therefore be addressed by the whole consortium, during the assessment of proposals for TNA services as well as breakthroughs in the innovation and in the joint research work packages. The role of TRANSVAC will be to unite relevant experts and regulators, to address emerging issues, and adopt new approaches through specific consultation workshops and meetings.

Partners

EVI logo
Name of partner institution: European Vaccine Initiative
Abbreviation of partner institution: EVI
Website of partner institution: www.euvaccine.eu
Contact email of partner: transvacinfo@euvaccine.eu

Description of partner institution

EVI is a non-profit Product Development Partnership supporting the development of vaccines for diseases of poverty by bridging conceptual and operational gaps in translational research. EVI supports strengthening of the vaccine R&D infrastructure in Europe, harmonisation, knowledge sharing, and aligning of major vaccine R&D stakeholders. EVI has extensive experience of almost 20 years in coordinating and participating in large scale infrastructure and collaborative research projects funded by the EC and other funders.

EVI’s mission is to lead European efforts to develop effective, accessible, and affordable vaccines against diseases of poverty. EVI’s vision is a world free of the intolerable burden of diseases of poverty within the coming decades'.

EVI’s main role in TRANSVAC is to handle the daily Coordination and Management of the project. This includes:

  • Coordination of project activities
  • Ensuring adherence to technical, financial, legal and contractual guidelines
  • Reporting project progress to the EC
  • Ensuring good communication within the project and with external stakeholders
  • Dissemination of the projects achievements
  • Managing the project’s Calls for Users
  • Managing the project’s external advisory committees, i.e. SEAC, USP and BoS

EVI also acts as the contact point between the European Commission and the consortium partners whilst connecting the project with as many external stakeholders as possible. The TRANSVAC Management Team is there to support the partners resolve any problems, and to provide them with guidance and advice wherever needed.

Name of main staff involved in the project

Dr. Odile Leroy Executive Director of EVI and TRANSVAC Project Coordinator

Dr. Hilde Depraetere Project Leader

Dr. Flavia D'Alessio Project Manager

Dr. Oliver Schraidt Project Manager

Dr. Nicola Viebig Project Manager Stakeholders

Sten Larsen Finance Director

A description of the Facility

EVI provides a fully equipped Project Management Office with its headquarters in Heidelberg, Germany.

TNA/training that will be provided

N.A.

Fraunhofer logo
Name of partner institution: Fraunhofer Institute for Molecular Biology and Applied Ecology IME
Abbreviation of partner institution: Fraunhofer
Website of partner institution: www.ime.fraunhofer.de
Contact email of partner: holger.spiegel@ime.fraunhofer.de

Description of partner institution

The Fraunhofer Institute for Molecular Biology and Applied Ecology IME is addressing different research areas in the field of applied life sciences, reaching from the molecular level towards complex ecosystems. The production and characterization of recombinant proteins using a large panel of different expression systems, including microbial systems, eukaryotic cells, as well as plants and plant suspension cells, is one of the IMEs main areas of expertise. The institute has more than 20 years of experience in the production of pharmaceutically relevant proteins of different types, covering vaccine candidates, cytokines, antibody fragments and full-length antibodies. These activities are being performed in the context of several public or industry-funded R&D projects, and the in house GMP-facility has been used for process development and production of clinical trial material in different expression systems, including E.coli, Pichia pastoris and transgenic tobacco plants.

Role of partner institution in project

The Fraunhofer IME leads the Transnational Access 1 (TNA1) "Cross platform screening and optimization service“ and the corresponding Joint Research Activity (JRA1) "Improved optimization and harmonization of cross-vector screening“ both aiming at the provision of comprehensive range of different well established pro- and eukaryotic expression/production systems to identify the optimal manufacturing platform for any given vaccine candidate. Within the Joint Research Activity (JRA3) Assay development and validation, Fraunhofer will work on the development and standardization of SPR-methods required during vaccine research and development as well as production and quality control, and on the development of impurity-related assays required for product characterization. In the context of the "European Training Programme in Vaccinology“ Fraunhofer IME will provide three different Training Modules including Assay Development and Validation, focused on SPR technology, Process Development and scale up, as well as on Requirements for GMP-production.

Name of main staff involved in the project

Holger Spiegel

Dr. Jürgen Drossard

Dr. Johannes Buyel

A description of the Facility

In addition to “state of the art” multipurpose S1 and S2 laboratory facilities, the Fraunhofer IME features a 100 m2 non-GMP process development laboratory with 5-30L stainless steel fermentation capacity. Additional cultivation systems including disposable systems from microtiter to 100L scale are available for general R&D and process development purposes. The GMP-production facility comprises two production suites with cleanroom classes D and C. One of the suites is designed for mammalian cell culture processes in that it has separate class C DSP rooms (pre/post virus inactivation). The upstream capacity is two trains of 15, 100 and 350 L working volume stainless steel bioreactors. Recovery and DSP equipment match the upstream capacity. Additionally the facility comprises greenhouse space as well as phytochambers for plant cultivation. Besides the whole range of standard technology for the purification and detailed characterization of biomolecules the facility is equipped with a molecular Interaction analysis suite including a GxP validated Biacore T200 SPR instrument.

TNA/training that will be provided

The Transnational Access 1 (TNA1) "Cross platform screening and optimization service“ and the corresponding Joint Research Activity (JRA1) "Improved optimization and harmonization of cross-vector screening“ will combine the expertise of six different partners (IME, SSI, UOXF, iBET, BPRC and UNISI) to provide the unique offer to test vaccine candidates in a comprehensive range of different expression hosts, to identify the optimal production system for further pre-clinical and clinical development. The development of SOPs and the implementation of standardized procedures wherever possible will enable the generation of reliable data on protein yields and quality to provide valid decision criteria on the choice of expression system. Within the "European Training Programme in Vaccinology“ Fraunhofer IME will provide two-day Training Modules focusing on three different topics. The module “Assay Development and Validation” will provide an insight into “state of the art” applications of SPR-technology in the context of vaccine development. Besides the detailed analysis of antibody responses, the training will address the development and validation of quality control and quantification assays. The training module “Process Development and scale up”, will give a deeper insight into the topic by discussing “real life” scenarios. Based on the experiences with several GMP-production processes, the module “Requirements for GMP-production” will improve the perception of essential prerequisites that have to be taken into account before heading for the “GMP” adventure.

SSI logo
Name of partner institution: Statens Serum Institut
Abbreviation of partner institution: SSI
Website of partner institution: www.ssi.dk
Contact email of partner: sowh@ssi.dk

Description of partner institution

Statens Serum Institut (SSI) is a public health institute, within the Ministry of Health in Denmark. SSI aims to ensure advanced control of infectious diseases, including new infectious and biological threats. The Institute also strives to be a highly regarded and recognized international research, and service enterprise.

Role of partner institution in project

The Statens Serum Institut (SSI) Center of Vaccine Research is internationally recognised for its vaccine research and clinical pipeline. This has yielded three Tuberculosis vaccine candidates undergoing phase IIa testing and three first-in-human trials of novel CMI-inducing adjuvants. The Center has developed and produced 15 different formulations for early clinical trials (e.g. vaccine antigens produced by heterologous expression) and has conducted more than 20 clinical trials as sponsor.

Name of main staff involved in the project

Peter Andersen, Vice-president and head of Vaccine R&D: Adjunct Professor of Immunology from the University of Copenhagen who has published more than 270 papers and 20 patents. He has organised and chaired many international meetings, given lectures all over the world and received numerous large national and international research grants. He heads several international research consortia, and was the most cited immunology researcher in Denmark 1990-2005.

Ingrid Kromann, Director: Chemical engineer with more than 20 years’ experience in vaccine development and quality control. She was responsible for the development of several new vaccines currently undergoing clinical trials and also has experience as a work package leader within large international consortia.

Dennis Christensen: Senior Scientist, Cand Pharm PhD, Formulation Scientist with more than 10 years experience in adjuvant design and evaluation. He is responsible Vaccine Adjuvant Research program at Statens Serum Institut. He has extensive experience with international vaccine-projects (e.g. EU sponsored TBVAC (FP6-7/H2020), ADITEC (FP7), BIOVACSAFE (IMI), UNISEC(FP7)) and with coordinating the research work in such projects including as WP leader.

Ida Svahn Rasmussen: Formulation Chemist, M.Sc., Involved in adjuvants.

Anders Vestermark: Protein Chemist, M.Sc., Involved in protein purification and downstream processing.

Charlotte Green Jensen: Laboratory Manager, PhD, Involved in molecular biology and fermentation.

A description of the Facility

The Center has a GMP pilot plant being able to produce recombinant antigens for vaccine formulations, formulation studies with the SSI CAF cased adjuvants is performed in laboratories using qualified equipment and procedures. The Center has access to state-of-the-art animal facilities including BSL3 containment, and has internationally renowned research programs on antigen discovery, the design and mechanism of CMI-inducing liposomal adjuvants, and the analysis of vaccine-induced immune responses.

TNA/training that will be provided

TNA1 Producing recombinant antigens using the E.Coli or L.Lactis production platform

TNA2: Formulation of vaccines using the SSI adjuvants CAF01 and CAF09b

TNA4: Production of recombinant antigens and final formulated vaccines for toxicological studies

TNA5: GMP production of recombinant antigen for vaccines

TNA8: Animal studies / TB mouse model

Information to follow shortly

LUMC logo
Name of partner institution: Leiden University Medical Center, Dept. Infectious Diseases
Abbreviation of partner institution: LUMC
Website of partner institution: www.lumc.nl/org/infectieziekten/Research
Contact email of partner: m.c.haks@lumc.nl, t.h.m.ottenhoff@lumc.nl

Description of partner institution

LUMC is a modern university medical center for research, education and patient care with a high quality profile and a strong scientific orientation. Its unique research practice, ranging from pure fundamental medical research to applied clinical research, places LUMC among the world top. This enables LUMC to offer patient care and education that is in line with the latest international insights and standards – and helps it to improve medicine and healthcare both internally and externally.

LUMC’s mission is to dissect host immunological and genetic mechanisms of protective and impaired immunity in infectious diseases. Its aim is to design optimal therapeutic (e.g. immune modulation) and preventive (e.g. vaccination) intervention strategies, by establishing relevant and robust biomarkers of disease and protection (e.g. immunodiagnostics and monitoring) and developing and testing new vaccines, and new vaccination strategies.

For more please see: https://www.lumc.nl/org/infectieziekten/Research/?setlanguage=English&setcountry=en

Name of main staff involved in the project

Marielle C Haks and Tom HM Ottenhoff

A description of the Facility

We provide access to a semi-high-throughput assay which is reliable, quantitative, robust, inexpensive, user friendly, and capable of profiling up to 200 genes using as little as 100 ng per sample. It allows the analysis of host immune gene expression in relation to vaccination, infection, disease or therapy in larger cohorts. We have incorporated genes that assess various compartments of the human immune response, which play key roles in inducing and skewing immune reactivity. Expression profiles can also be determined following relevant antigenic in vitro stimulation using whole blood or PBMC-based assays with samples derived from individuals/patients collected at different time points post vaccination /immunisation. The facility is already used by other EU projects.

TNA/training that will be provided

Modality of access under this proposal: Users will provide either samples or ready-isolated RNA and will decide how many genes will be profiled. Analysis of gene expression profiles can be carried out by the users, or by the facility. Users can be trained at the facility if needed. A maximum of seven projects can be supported under this service, depending on sample numbers.

Support offered under this proposal: Extended multiplex transcriptome profiling (dcRT-MLPA) of innate, adaptive and inflammatory immune-response signalling gene signatures. In mutual agreement with the facility, users will decide the scope of the service, including the number of genes to be profiled.

IDMIT logo
Name of partner institution: IDMIT Infrastructure (CEA)
Abbreviation of partner institution: CEA
Website of partner institution: www.idmitcenter.fr
Contact email of partner: roger.le-grand@cea.fr

Description of partner institution

The mission of “infectious diseases models and innovative therapies” (IDMIT) infrastructure is to provide the scientific community with an exceptional capacity in Europe for human infectious diseases preclinical research. The partner founders of IDMIT include major institutions in the field of human health and infectious diseases - the CEA, also coordinator of the infrastructure, the Insitut Pasteur, the INSERM, the Paris-Saclay and Paris-Sud Universities, and the Nation Agency for AIDS Research and Viral Hepatitis (ANRS) – covering research areas from basic science and technological innovation to medicine. IDMIT hosts technical and scientific staff with unique expertise and centralises in a single location large facilities for NHP models (as an example: AIDS, Influenza, Pertussis, chlamydia infections, arboviruses, Ebola vaccines), in vivo imaging and core laboratories.

Role of partner institution in project

IDMIT will contribute 1) To the development and validation of assays based on flow cytometry and mass cytometry for the evaluation of immune responses in humans and animal models; these tools will be particularly relevant for the identification of signatures of vaccine efficacy; 2) To the animal model platform, in particularly by providing access to NHP models and to new technologies for in vivo imaging infections and host responses; 3) To networking activities, in particular by organising a workshop on in vivo imaging.

Name of main staff involved in the project

Roger LE GRAND (Ph.D., D.V.M.): Director of IDMIT infrastructure

Nathalie DERREUDDRE-BOSQUET (Ph.D.): Director of IDMIT core laboratory for immunology and infectiology

Antonio COSMA (Ph.D.): Director of IDMIT FlowCyTech Core laboratory

Catherine CHAPON (Ph.D.): Director of IDMIT core laboratory for In vivo Imaging of Infection and Immunity

Christophe JOURBERT (Ph.D./ D.V.M.): Director of IDMIT Animal Science and Welfare core facility

A description of the Facility

IDMIT is an infrastructure for preclinical research in infectious diseases and immunology which is certified ISO9001 and which includes 1) A large animal facility with capacity to host NHP in BSL2 and BSL3 containment, 2) State-of-the-art laboratories for cell biology, immunology, molecular biology, flow cytometry and mass cytometry (CyTof), cell-sorting and confocal microscopy in BSL3 containment; 3) A biological resources centre with high storage capacity; 4) Highly innovative technologies for in vivo imaging of large animals in BSL2 and BSL3 containment, including a two-photon microscope, a PET-CT facility, and several optic based technologies (fibered endo-microscopy, near infra-red imaging).

TNA/training that will be provided

IDMIT will provide access to flow cytometry and mass cytometry technologies with no species limitation. In addition, IDMIT offer access to preclinical immunogenicity studies using NHP and access to its BSL2 and BSL3 in vivo imaging core facilities (PET-CT, Two-photon microscope, NIR technologies, and fibered endo-microscopy).

SWR logo
Name of partner institution: Wageningen Bioveterinary Research, part of Wageningen University&Research
Abbreviation of partner institution: SWR
Website of partner institution: www.wur.nl/nl/Expertises-Dienstverlening/Onderzoeksinstituten/Bioveterinary-Research.htm
Contact email of partner: info.bvr@wur.nl

Description of partner institution

Wageningen Bioveterinary Research (WBVR) is part of Wageningen University&Research (WUR/SWR), a Dutch organisation combining academic institutes and research institutes in the field of life sciences. The broad spectrum of university and research institutes enables innovative, multidisciplinary approaches by close collaborations. WBVR contributes to the prevention, eradication and control of animal infectious diseases through research, diagnostics and consultancy. This is essential to guarantee international trade and to preserve the international top position of the Dutch livestock industry. A specific focus of WBVR is research on infection biology, immunology and vaccinology of relevant veterinary and human, current and emerging infectious diseases. About 200 highly-qualified and devoted personnel work at WBVR and provide extensive experience for microbiological, immunological and genomic research, including bioinformatics. WBVR has broad experience in co-operation with private partners and EU infrastructure projects by offering facilities and expertise in animal studies with laboratory and large animal models. Expertise concerns vaccine immunogenicity, vaccine efficacy and infectious disease pathogenesis.

Role of partner institution in project

In this project WBVR of SWR performs research on improvement of animal models for vaccine research specifically in neonate conditions. Next to this, WBVR offers the use of its infrastructure to perform immunogenicity and efficacy studies for newly developed vaccines.

Name of main staff involved in the project

Dr. Norbert Stockhofe-Zurwieden

Dr. Rineke de Jong

A description of the Facility

WBVR as part of SWR is equipped with state-of-the-art laboratory and animal facilities for microbiological and immunological testing of vaccines. The animal facilities can accommodate the entire range of species, including farm animals for studies under containment (up to BSL3) and complies with ISO standards (9001:2008, 17025). Vaccine studies are supported by bacteriology and virology expertise and a range of immunological assays for various lab animal (mouse, ferret) and farm animal species (cattle, pig, chicken).

TNA/training that will be provided

WBVR of SWR offers access to their infrastructures and expertise for the testing of new vaccines. Based on their expertise in immunology and pathology and the available infection models, vaccines against most relevant viral and bacterial animal infections can be tested. Depending on the availability of the appropriate animal model, WBVR also offers to study vaccines against human pathogens.

ECRIN logo
Name of partner institution: European Clinical Research Infrastructure Network
Abbreviation of partner institution: ECRIN
Website of partner institution: www.ecrin.org
Contact email of partner: christine.kubiak@ecrin.org

Description of partner institution

The European Clinical Research Infrastructure Network (ECRIN, www.ecrin.org) is a sustainable, not-for-profit, distributed infrastructure with the legal status of a European Research Infrastructure Consortium (ERIC).

ECRIN provides support for the development and implementation of multinational clinical research projects in Europe.

ECRIN currently has seven Member Countries (France, Germany, Spain, Italy, Portugal, Hungary and Norway) and two Observer Countries (Czech Republic and Switzerland). Additional countries are about to join.

ECRIN focuses on multinational academic research as well as trials initiated by biotech and medical device small and medium enterprises (SMEs). It provides support to sponsors in investigator-initiated trials and helps them navigate Europe’s fragmented health and legal systems. Multi-country trials means greater access to patients, resources, and expertise, and, in turn, faster and potentially more robust results.

Role of partner institution in project

ECRIN will provide consultancy services for vaccines clinical trials development. In particular ECRIN will provide all the necessary information regarding the regulatory and ethical requirements necessary for a specific clinical trial. ECRIN will provide access to methodological experts for advice and the review of the clinical protocols. Consultancy will also be offered for the development of funding applications and especially for all aspects regarding the organisation of the management and logistical aspects of multinational clinical trials. In addition ECRIN will provide through its national scientific partners services within the management of the clinical trials and in particular the regulatory and ethical submissions in multiple countries.

Name of main staff involved in the project

Christine Kubiak, Operations Director

A description of the Facility

ECRIN’s ‘distributed infrastructure’ includes a Core Team based in Paris, France (headquarters) and European Correspondents (EuCos) working in country. ECRIN brings together scientific partners that are national networks of academic clinical trial units (CTUs) and/or clinical research centres (CRCs) located at or affiliated to national universities and hospitals. These CTUs/CRCs have professional staff specialised in clinical research and are highly qualified to conduct multinational clinical trials according to international standards, general and specific regulations applying to clinical trials, and Good Clinical Practices.

ECRIN provides services for the management of multinational trials after having supported investigators and sponsors in the preparation of the trial protocol and funding application, and after validation of the trial through independent protocol peer-review and logistical assessment.

Services during the conduct of the trial include central services (data management through ECRIN certified data centres, central vigilance) and distributed services provided by the ECRIN partner in each country involved (regulatory and ethical submissions and follow-up, monitoring, local vigilance, etc.).

ECRIN primarily provides support to sponsors in investigator-initiated trials; its focus is on independent, multinational academic research as well as trials initiated by biotech and medical device small and medium enterprises (SMEs).

TNA/training that will be provided

ECRIN will provide, for multinational clinical trials, regulatory and ethical submissions in the different countries participating in the trial using the ECRIN national infrastructures in the countries involved.

This includes the adaptation of the protocol to national requirements, preparation and adaptation of the patient information sheet and informed consent form, preparation of the documentation required for submission to Ethics Committees and Competent Authorities, submission of the clinical trial Application dossier (CTA) and regulatory follow-up.

EATRIS logo
Name of partner institution: European Infrastructure for Translational Medicine
Abbreviation of partner institution: EATRIS
Website of partner institution: eatris.eu/
Contact email of partner: info@eatris.eu

Description of partner institution

EATRIS is a European Research Infrastructure Consortium (ERIC) founded to defragment the European substantial efforts in translational research. Its mission is to improve productivity of the translational R&D pipeline by providing high quality research services to public and private research entities. Comprising over 80 leading research institutions located in twelve countries across Europe, EATRIS has been a key player in the biomedical innovation continuum.

By bringing together multi-disciplinary expertise, facilities and patient resources to support the development of promising drugs and diagnostics, EATRIS accelerates and de-risks the path to clinical proof of concept and partners with key stakeholders for the validation and introduction of novel tools to support R&D.

Role of partner institution in project

EATRIS involvement in TRANSVAC2 will include primarily the development of a regulatory platform for preclinical, marketing authorisation and pharmacovigilance for clinical trials. In addition, EATRIS will seek to identify inconsistencies in the national regulatory frameworks while offering consultation on preclinical vaccine development (WP16).

Additionally, EATRIS will be leading a task to secure the long-term sustainability of the vaccine infrastructure and will be actively involved in the drafting of a business plan in order to mobilise the necessary support for the further implementation and ultimately the long-term operation of the infrastructure.

Name of main staff involved in the project

David Morrow, Vaccines Platform Manager, EATRIS-ERIC

Jiri Deml, Regulatory expert, Brno University (Linked third party of EATRIS)

Lucia Gabriele, Research leader, ISS (Linked third party of EATRIS)

A description of the Facility

The infrastructure consists of non-profit research institutes that engage in collaborative research and services in the translational phase of preventive, diagnostic and therapeutic product development. EATRIS offers the entire spectrum of high-end research infrastructure and patient cohorts all accessible though just one portal, and maximises product potential by providing support from discovery to clinical trials. The services offered cover the areas of advanced therapy medicinal products, biomarkers, imaging and tracing, small molecules and vaccines. The EATRIS vaccines platform offers services covering the entire vaccine development and production pipeline ranging from late-phase pre-clinical development to clinical trials, and comprises fourteen institutions.

TNA/training that will be provided

EATRIS will develop a training workshop dedicated to regulatory aspects of vaccine development that will be delivered twice over the project’s lifetime. Participants will learn how to plan a regulatory strategy from the early phases of development and prepare a well-organised dossier in a changing regulatory environment.

Name of partner institution: Vaccine Formulation Institute
Abbreviation of partner institution: VFI
Website of partner institution: www.vformulation.org
Contact email of partner: maria.lawrenz@vformulation.org

Description of partner institution

Adjuvants are frequently used by the vaccine research and development community, primarily for their ability to modulate immune responses and improve dose-sparing. However, suitable adjuvants and the associated expertise required to effectively use them are not readily available to the majority of vaccine research groups. Even those groups with access to suitable adjuvants frequently fail in the development of their adjuvanted vaccines because of a lack of knowledge on how to correctly formulate and characterize both their adjuvants and the resulting vaccine formulations. These challenges led to the creation of the Vaccine Formulation Institute (VFI) in 2012, which today provides a variety of adjuvant-related laboratory and training services to the vaccine community. The VFI aims to provide access to a wide variety of adjuvant technologies and to improve access to advanced formulation expertise and quality control assays on a not-for-profit basis to all interested groups.

Role of partner institution in project

VFI will lead the coordination of TRANSVAC2 training activities. This will include the development of procedures for training advertisement, application and selection processes, and in close collaboration with the consortium partners, the development of a comprehensive training program in vaccinology, consisting of short modules that can be combined to customized courses.

Furthermore VFI will organize the training module on Adjuvants and Vaccine Formulation.

Name of main staff involved in the project

Dr. Maria Lawrenz

A description of the Facility

The Vaccine Formulation Institute has access to laboratories and training facilities, including at University of Lausanne, Switzerland.

TNA/training that will be provided

Training Module - Adjuvants and vaccine formulation:

This four-day module for up to ten participants will be organized by VFI in collaboration with UNIL and SSI (Technology Platform). The course will combine lectures with laboratory demonstrations, discussion rounds and group work on thematic case studies. The focus of this training module will be the different vaccine adjuvant systems and best practices in formulation of adjuvanted vaccines.

UOXF logo
Name of partner institution: University of Oxford
Abbreviation of partner institution: UOXF
Website of partner institution: www.ox.ac.uk and www.jenner.ac.uk/home
Contact email of partner: rebecca.ashfield@ndm.ox.ac.uk

Description of partner institution

The Jenner Institute is part of the University of Oxford. It was founded in November 2005 to develop innovative vaccines against major global diseases. Uniquely it focuses both on diseases of humans and livestock and tests new vaccine approaches in parallel in different species. A major theme is translational research involving the rapid early-stage development and assessment of new vaccines in clinical trials. The Institute is a partnership between the University of Oxford and the The Pirbright Institute and is the successor to the former Edward Jenner Institute for Vaccine Research.

The Institute comprises the research activities of over 30 Jenner Investigators who head leading research groups spanning human and veterinary vaccine research and development. Together the Institute Investigators comprise one of the largest non-profit sector research and development activities in vaccinology.

Jenner Institute Investigators, through the support of many funders, are developing new vaccine candidates against major global infectious diseases. New vaccines against malaria, tuberculosis and HIV are currently in field trials in the developing world. Research is also underway on livestock vaccines against foot and mouth disease, avian influenza, bovine tuberculosis and other major causes of economic loss.

Role of partner institution in project

The Jenner Institute (University of Oxford) will participate in three areas of TRANVAC2:

  • Firstly, it will develop optimised viral vectors suitable for expressing antigens from a range of different diseases, to create novel vaccines. The vectors used are replication-incompetent Adenovirus or MVA (Modified Vaccinia Ankara), usually used in combination as a prime-boost dosing strategy. Both vectors induce high levels of antibody and T cell responses. Virally vectored vaccines expressing novel antigens will be provided as TNA activities.
  • Secondly, the Jenner will develop its transcriptomics core facility to carry out RNAseq analysis of clinical samples (both blood and bronchoalveolar lavage fluid) from trials with novel TB, malaria and Ebola vaccines. Bioinformatics analysis is a particular strength at the Jenner, and will be offered as part of the TNA activities.
  • Thirdly, the Jenner runs three vaccinology courses annually, two in Oxford and one in Africa. Places on the Oxford courses will be offered as part of the TRANSVAC2 training workpackage. The Oxford courses specialise in vaccine biomanufacturing, clinical development, and human/veterinary vaccinology.

Name of main staff involved in the project

Professor Adrian Hill (Viral Vector Vaccines)

Professor Helen McShane (Transcriptomics)

Dr. Rebecca Ashfield (Vaccinology Training)

A description of the Facility

The Viral Vector Core Facility produces recombinant virus-vectored vaccines for pre-clinical validation experiments and GMP starting material. The facility routinely produces human and primate Adenovirus (Ad) and MVA vectors and its capability will soon expand to include other viral vector backbones, such as adeno-associated virus (AAV). Virus-vectored vaccines are produced at high yields with appropriate QC, and are suitable for antigen screening in animal models. Services currently offered by the infrastructure: The facility currently produces MVA and human/primate Ad vectors for any external user who applies for the service on a fixed cost per virus basis. Services include the construction of new recombinant viral vectors, and bulking up existing vectors. QC includes virus titration, confirmation of identity, and sterility.

The Transcriptomics Core Facility supports a systems biology approach in vaccine development focusing on the identification of transcriptomic correlates of vaccine immunogenicity and efficacy for a range of novel and licensed vaccines using PBMC or whole-blood and BAL fluid samples. Services include advice on sample selection and experimental design, design of protocols and templates, RNA extraction, quality assessment and amplification, and library construction for RNA sequencing. Bioinformatics services include data QC, outlier detection and general data management, and data analysis from platforms including Illumina or Affymetrix microarrays, RNA-Seq, SNP arrays, Exome-sequencing, ChIP-chips and CHIP-seq.

TNA/training that will be provided

1. The Jenner will provide up to 40 vectored vaccines as part of the TRANSVAC2 TNA activities, which will be GMP compliant if required.

2. The Jenner will provide RNAseq and/or bioinformatics analysis of pre-existing transcriptomics data for up to 200 samples from vaccine clinical trials.

3. The Jenner will provide 20 places on each of 3 courses: a) basic immunology, b) vaccine clinical development and biomanufacturing, and c) human and veterinary vaccinology.

iBET logo
Name of partner institution: Instituto de Biologia Experimental e Tecnológica
Abbreviation of partner institution: iBET
Website of partner institution: www.ibet.pt
Contact email of partner: marques@ibet.pt

Description of partner institution

IBET is a private non-profit research-intensive institution founded in 1989 with the mission to integrate and strengthen biological and biochemical knowledge from its academic and industrial partners and transfer technology to the market. IBET brings together, as partners and collaborators, private companies and public institutions, creating a critical mass of competencies for product and process development. Science and technology are used to accelerate the translational application of competences from early-stage discovery to final production and processes. iBET’s know-how, in terms of biopharmaceuticals, spans from the initial expression vector design and cell line establishment through all stages of process development and scale-up (production, purification, stability and storage). IBET has coordinated more than 30 international projects, has participated as a work package leader in more than 50 EC projects, and has also carried out many further projects for industry clients. Recently, iBET became the coordinator of a research unit funded by FCT, iNOVA4Health, a translational medicine program organising the efforts of biomedical researchers involved in biological understanding of disease, lead compounds and biopharmaceuticals (pre-discovery), technological scientists involved in preclinical development, and clinicians involved in early clinical and first-in-man clinical trials.

Role of partner institution in project

IBET will be represented by senior experts from its Animal Cell Technology Unit (ACTU). One of the focus areas of the ACTU is rational process development for complex biopharmaceuticals, in particular the production of vaccine candidates (e.g. subunit recombinant proteins, viruses and virus-like particles - VLPs) for human and veterinary use based on insect and mammalian cell lines. These activities have been developed within both EC-funded and industry-funded projects, involving large companies (Novartis, MSD) and small start-ups (LETI, ALLOKSYS, VCN, GENETHON, CEVEC). Competencies include upstream and downstream processing, where IBET has also participated in developing and testing single-use equipment for Sartorius-Stedim Biotech, GE Healthcare, Merck Millipore, PALL and LONZA.

iBET will be involved in WP7 (cross-platform screening and optimisation service) and WP10 (pre-clinical GLP production services). In WP7, iBET will be involved in activities connected with mammalian and insect cell expression platform screening, and small-scale production and purification of candidate vaccines. In WP10, iBET will be involved in the GMP-directed evaluation of vaccine candidate production processes, production scale-up for vaccine candidates, definition of specifications for pilot-scale production, product stability testing and delivery for GLP toxicology studies, as well as the evaluation of development, manufacturing and finishing documentation.

Name of main staff involved in the project

Paula Alves (iBET CEO and ACTU Director)

Manuel Carrondo (Founder and former CEO of iBET, Professor of Chemical and Biochemical Engineering, Head of the Engineering Cellular Applications Laboratory ACTU)

António Cunha (iBET Pilot Plant Director)

Ana Sofia Coroadinha (Head of ACTU Cell Development Laboratory)

Cristina Peixoto (Head of ACTU Downstream Process Laboratory)

Antonio Roldao (PhD and responsible for the ACTU Vaccine Area)

A description of the Facility

iBET’s infrastructure comprises 16 laboratories fully equipped with state-of-the-art technology (70 m2 each), including a BSL2 laboratory for working with viruses; a GMP Analytical Services Unit certified by the INFARMED (the Portuguese medicines authority, EMA Portuguese branch) and by DGAV (the Portuguese veterinary authority) for quality control and batch release of human and veterinary pharmaceuticals, biopharmaceuticals as well as experimental new drugs; a GMP Mass-Spectroscopy Unit that provides state-of-the-art MS services to the scientific community and Industry; a 2600 m2 bio-pilot plant supporting production and purification of proteins ATMPs and vaccines from bench top to 300 L scale and privileged access to GeniBET Biopharmaceuticals, an iBET spin-off producing ATMPs under cGMP certification for phase I/II/III clinical trials.

Supporting researchers, iBET has a core Infrastructural Unit, including an Administrative Department that deals with all aspects of administrative and financial support to research projects and contracts with the industry, including support in technology transfer and intellectual property rights; a Marketing and Business Development Department and a Human Resources and People Development Office.

TNA/training that will be provided

iBET will be involved in WP7 (cross-platform screening and optimisation service) and WP10 (pre-clinical GLP production services).

In WP7, iBET will be involved in activities relating to mammalian and insect cell expression platform screening, and small-scale production and purification of candidate vaccines.

In WP10, iBET will be involved in activities relating to GMP-directed evaluation of vaccine candidate production processes, production scale-up for vaccine candidates, definition of specifications for pilot-scale production, product stability testing and delivery for GLP toxicology studies, as well as the evaluation of development, manufacturing and finishing documentation.

GEN logo
Name of partner institution: GenIbet Biopharmaceuticals
Abbreviation of partner institution: GEN
Website of partner institution: www.genibet.com
Contact email of partner: info@genibet.com

Description of partner institution

GenIbet is a biopharmaceutical CDMO (Contract Development and Manufacturing Organization) offering highly specialized microbial, cell culture and viral propagation process development and cGMP manufacturing services to research groups, biotech and pharma companies. This, combined with in-house fill and finish capabilities, gives our clients the opportunity to go from bench to clinic in one facility. GenIbet’s core activity is the manufacture and supply of materials for use in early stage drug development, pre-clinical studies and cGMP manufacturing from Phase I to Phase III clinical trials.

Our services

  • Process development for biopharmaceuticals
  • cGMP biopharmaceutical production (drug substance and drug product)
  • cGMP master and working cell bank production
  • cGMP master and working virus seed stock production
  • cGMP cell and gene therapy production
  • Fill and finish
  • Quality control and quality assurance services

Role of partner institution in project

Manufacture of GMP master/working cell banks

Manufacture of GMP master/working virus seed stocks

Manufacture of clinical-grade vaccine candidates (drug substance and drug product)

Name of main staff involved in the project

Raquel Fortunato, PhD (CEO)

Tiago Ferreira, PhD (Operations and Planning Director)

A description of the Facility

GenIbet offers 1000 m2 of GMP-compliant upstream and downstream manufacturing facilities, including QC labs and R&D facilities, three BSL2 units for the cultivation of bacterial cells (50 L capacity), insect and mammalian cells (50 L capacity for suspension cell cultures, 168,000 cm2 capacity for adherent cells) and the propagation of viruses (50 L capacity, with space to expand up to 200 L). GenIbet has also manual filling capacity of up to 1500 vials with volumes of 0.1 to 100 ml.

TNA/training that will be provided

GenIbet provides GMP production Services that can be accessed on a pay-per service basis.

HZI logo
Name of partner institution: Helmholtz Centre for Infection Research
Abbreviation of partner institution: HZI
Website of partner institution: www.helmholtz-hzi.de/en/
Contact email of partner: Carlos.Guzman@helmholtz-hzi.de

Description of partner institution

The Helmholtz Centre for Infection Research (HZI) is a member of the Helmholtz Association, the largest scientific organization in Germany bringing together 18 scientific-technical and biological-medical research centres. The mission of the HZI, with its main campus in Braunschweig, is to rise to the societal challenges of infectious diseases by investigating their fundamental mechanisms of pathogenesis. For this, research focuses on three main topics: “Bacterial and viral pathogens”, “Immune response and immune interventions” and “Anti-infectives”. The key questions that the scientists at the HZI address are: How do bacteria and viruses make us sick? How does the immune system fight these pathogens? And which substances can protect us from infections in the future? The ultimate aim is to derive innovative approaches for the prevention, diagnosis and therapy of infectious diseases. To ensure the most effective translation of basic research results to application, the HZI also intensively collaborates with clinical partners. The centre employs around 900 employees from various professional sectors, originating from over 40 countries, and has an annual budget of over 50 million euros (2016).

Role of partner institution in project

The HZI will provide expertise and technologies for adjuvants and the preclinical validation of vaccine technologies and candidates in murine systems. The HZI will develop a vaccination protocol for mucosal administration based on three novel strategies: (i) development and optimization of a vaccination protocol in which parenterally-primed T and B cells are subsequently pulled into the mucosa by the local delivery of the cognate antigen to the requested effector site, (ii) testing the co-administration of antigens with novel mucosal adjuvants using different mucosal immunisation routes and schedules, and (iii) testing various nanoparticles co-administered with different immunomodulators for their ability to generate both systemic and mucosal immune responses following transcutaneous/trans-follicular vaccination. Selected mucosal vaccine candidates as well as additional novel adjuvant formulations will be tested for immunogenicity in mice. Furthermore, the mode of action of different adjuvant and antigen formulations will be studied, with the overall aim to develop adjuvant formulations ready for pre-clinical and ultimately clinical development.

The HZI will also not only perform experiments to compare the predictive immunogenicity and efficacy of vaccines between different model species and humans but will test comparative effects of adjuvants.

Finally, the HZI will help develop in vivo imaging technologies to characterize (i) vaccine biodistribution and persistence, and (ii) cellular and molecular changes at the injection site and in draining lymphoid tissues, helping to refine the use of animal models.

Name of main staff involved in the project

Prof. Carlos A. Guzmán, MD. PhD

Dr. Thomas Ebensen

Dr. Kai Schulze

Dr. Peggy Riese

Dr. Blair Prochnow

A description of the Facility

The scientific work at the HZI Department of Vaccinology and Applied Microbiology includes the elucidation of mechanisms of host responses to infection and vaccination, discovering new mucosal adjuvants, and developing and validating vaccines against specific infectious diseases. For this, conventional and advanced murine models are ideally suited to perform a cost-efficient screening, selection and prioritization of vaccine candidates.

The department features expertise, technology and infrastructure in the fields of adjuvants, immune modulators and formulation, including mucosal adjuvants. Our experts in mucosal vaccine delivery have established in vitro and in vivo models to assess the activity of adjuvants and vaccine formulations on innate and adaptive immune cells, as well their capacity to stimulate different effector mechanisms of clearance. The team has access to state-of-the-art laboratories and animal facilities with BSL2 and BSL3 containment, flow cytometry, cell sorting, histopathology and in vivo imaging (IVIS).

TNA/training that will be provided

The HZI will provide access to its formulation and characterization services for candidate antigens paired with mucosal adjuvants. The service will include formulation, stability testing and the physicochemical characterization of adjuvants and vaccines, including advanced immune system monitoring.

This service will allow users to improve the compatibility and stability of their vaccine antigen with different mucosal adjuvants (from the HZI portfolio) and to define the optimal production methods to generate immunogenic vaccine candidates with optimised physicochemical stability (in vitro studies). A summary of the results obtained with each formulation will be provided. Material suitable for preclinical in vivo immunisation studies will be provided to the customer. The HZI will also provide access to laboratory and animal facilities up to BSL3 and conventional, modified (e.g. knockout, knock-in, reporter) and humanised (e.g. immune system) mice as animal models. We will evaluate the immunogenicity of vaccine candidates (provided by user) administered by systemic, transdermal or mucosal routes and will monitor humoral responses and cellular responses. We offer challenge studies with conventional and humanized mice including animal health and pathogen monitoring. We also offer passive cell transfer studies, generation of bone marrow chimeras, in vivo imaging (IVIS), determination of the microbiome, and histopathology.

BPRC logo
Name of partner institution: Biomedical Primate Research Centre
Abbreviation of partner institution: BPRC
Website of partner institution: www.bprc.nl
Contact email of partner: verreck@bprc.nl

Description of partner institution

BPRC is an independent non-profit research foundation with self-sustaining breeding colonies of macaques (Macaca spp.) and common marmosets (Calithrix jacchus). The mission of BPRC is to perform fundamental and applied research using non-human primates, with the aim to identify, develop and test new vaccines and medicines for diseases that cause misery and large numbers of deaths in the human population worldwide and only when there are no suitable alternatives. BPRC also has an active programme to develop alternatives for animal experiments following the ethical principles of reduction, refinement and replacement (3Rs). BPRC housing and animal care procedures comply with Dutch law, European Directive 2010/63/EU, and with the “Standards for Humane Care and Use of Laboratory Animals by Foreign Institutions”, identification number A5539-01, provided by the Department of Health and Human Services of the US National Institutes of Health. BPRC is AAALAC accredited.

Role of partner institution in project

BPRC is involved in research and training activities and provides access to several aspects of vaccine development within TRANSVAC2. Research activities are focussed on the development and validation of state of the art assays for protein expression systems and the structural and functional characterization of vaccine candidates. BPRC is also involved in the development of assays and biomarkers for the predictive value of animal models in vaccine evaluation.

BPRC provides access to 1) P. pastoris based protein expression systems, 2) cell-based reporter assays for characterization of innate immune receptor induced signalling cascades, and 3) macaques for immunogenicity/adjuvanticity evaluation of vaccine candidates for diseases such as malaria, tuberculosis, HIV, influenza, West Nile virus, Zika virus, Rift Valley fever virus or dengue virus.

Training on statistics of vaccine evaluation is offered.

Name of main staff involved in the project

J. Langermans: PhD in immunology and almost 20 years of experience in the use of NHP models and infectious disease research. He has also been involved in vaccine research using small and large animal models, e.g. pigs. He collaborates in many EU international consortia, is chairman of the EATRIS Vaccines Platform, chairman of the scientific board of IDMIT and ethics advisor in various EU programs using animals for research.

F. Verreck: PhD in immunology and over 10 years of experience in using NHP models for basic and applied research objectives in vaccine development and TB in particular. He has collaborated in several international consortia on vaccine development and has managed/manages EC projects under FP6, FP7 and Horizon2020. He is a member of the management team of the Tuberculosis Vaccine Initiative (TBVI).

C. Kocken: PhD in molecular biology and over 20 years of experience in malaria NHP models for drug and vaccine development. He has collaborated in many FP 5, 6 and 7 programmes. He has been Board member and treasurer of the Dutch Society for Parasitology and is currently chairing the Board of the European Vaccine Initiative (EVI).

W. Bogers: PhD in immunology and 20 years of experience with NHP models for the preclinical evaluation of HIV vaccine candidates as well as testing antivirals. He has collaborated in several international consortia on vaccine development and managed projects under FP5, 6 and 7, NIH HIVRad-I/II, and the Bill & Melinda Gates Foundation (BMGF).

G. Koopman: PhD in immunology and 18 years of experience in vaccine research in NHPs, focusing on HIV and influenza vaccines and antigen presenting cell function. He has coordinated FP5 and 6 projects and has collaborated in several international consortia on HIV vaccine development.

E. Remarque: PhD in immunology and over 20 years of experience in vaccinology, focusing on how the immune system responds to polymorphic antigens. He is involved in several EU-funded vaccinology projects (e.g. TRANSVAC, EMVDA, EduFluVac) and has a strong background in immunology, statistics and methodology.

J. Bajramovic: PhD in immunology and over 10 years of experience in innate immunology and neuroscience. He has extensive experience in in vitro methodology to model immune responses and work package coordination.

B. Faber: PhD in biochemistry, working for almost 20 years with fungal, yeast and bacterial protein expression systems. He has used his experience in molecular techniques and protein purification/characterisation in a number of malaria vaccine projects (EuroMalvac, EMVDA) and the design and optimisation of GMP compliant subunit vaccine production.

K. Haanstra: PhD in immunology and 20 years of experience with NHP models of chronic disease and macaque immunology. She has extensive experience in experimental animal study design and work package coordination.

A description of the Facility

At BPRC non-human primate (NHP) models of infectious diseases are available in high quality, using purpose-bred and MHC-typed animals. Animals are housed in up-to-date facilities, complying with international and legal standards at biocontainment level BSL2 and BSL3. Expert scientific, veterinary, surgical and biotechnical support is provided to the users of the facility. Animal health is monitored in house, with services for microbiology, pathology and haematology/serum chemistry available at biocontainment level ML2 and ML3. Facilities for PET-CT, in situ data-logger expertise and equipment for non-invasive quantification of disease progression and therapeutic intervention is available. Expert scientific support is available for immunology and immunopathology research in NHP, for monitoring of cellular and humoral immune-reactivity, ELISA, ELISPOT and Luminex technology for ex vivo cytokine production, flow-cytometry and FACS sorting, and immunohistochemistry.

TNA/training that will be provided

TNA1: BPRC will provide access to its P. pastoris systems, which allow the constitutive or inducible expression of intracellular or secreted proteins. BPRC will also provide P. pastoris strains overexpressing chaperone/helper proteins to boost expression levels.

TNA3: BPRC will offer access to its library of human cell reporter assays for the identification of innate immune receptor-induced signalling cascades, including human cell lines transfected with PAMPs such as TLR and/or engineered to express luciferase in response to NF-kB or IFRE-mediated signal transduction, and cell lines that provide insight into the intracellular signalling cascades of innate immune receptors. These lines allow for qualitative and quantitative assessment of innate immune responses provoked by different stimuli, resulting in innate immune response fingerprints.

TNA8: BPRC will provide access to macaques for immunogenicity/adjuvanticity evaluation of vaccine candidates for malaria, tuberculosis, HIV, influenza, West Nile virus or dengue virus, with up to three (prime-boost) immunisation events. The service includes baseline assessments and post-vaccination follow-up by biosample collection, as well as standard and/or user specific humoral and/or cellular immunology tests. Additional study objectives, such as challenge or advanced immunological assessments or imaging, may be discussed.

NA3: BPRC will provide a five-day module on Statistics of vaccine evaluation. It will address statistical and methodological topics for the pre-clinical and clinical evaluation of vaccines and includes lectures followed by hands-on training.

LSHTM logo
Name of partner institution: London School of Hygiene and Tropical Medicine
Abbreviation of partner institution: LSHTM
Website of partner institution: www.lshtm.ac.uk
Contact email of partner: hazel.dockrell@lshtm.ac.uk; steven.smith@lshtm.ac.uk

Description of partner institution

LSHTM is a leading postgraduate institution for research and teaching in public and global health.

It is the largest institution of its kind in Europe with a wide depth and breadth of expertise encompassing many disciplines. It is the world’s leading research-focussed graduate school, and ranked four in the world for research citations and in the top 100 universities worldwide for reputation. Its mission is “To improve health and health equity in the UK and worldwide”, working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice. LSHTM has active cross disciplinary research centres for vaccines with over 100 personnel, and has the largest grouping of researchers working on TB in Europe.

Role of partner institution in project

The role of LSHTM in the TRANSVAC2 project is to develop a sensitive human whole-blood assay to compare the potency of whole vaccines and vaccine antigens based on their ability to induce innate and adaptive cytokine and chemokine responses. These responses will be quantified using both commercial and customised Luminex bead arrays. Once developed, the assays will be used to analyse in vitro cytokine and chemokine induction, e.g. to compare different versions of a vaccine, or the same vaccine produced in different host cells, or different batches of a vaccine to demonstrate batch-to-batch reproducibility. Transnational access to this assay will then be provided.

Name of main staff involved in the project

Professor Hazel M Dockrell

Dr Steven G Smith

A description of the Facility

The Immunology laboratories offer Luminex facilities (including access to Luminex 100/200 and Magpix instruments). The group has over 10 years’ experience with this methodology, with specific expertise in cytokine/chemokine detection in tissue culture supernatants and plasma samples with panels containing up to 42 analytes. The group also has experience in the creation of custom panels for the analysis of pathogen specific immune responses with focus on innate and adaptive arms of the immune system.

TNA/training that will be provided

LSHTM will provide a whole-blood assay to compare the potency of vaccine candidates based on their ability to induce innate and adaptive cytokine and chemokine responses, detected by capturing the signalling molecules on customised or commercial Luminex bead arrays. This will be used to confirm the potency of vaccine candidates in a human immune system model, to compare different vaccines or the same vaccine produced in different expression hosts, or to ensure consistent production quality and batch-to-batch reproducibility, including the viability of live whole cell vaccines.

DH logo
Name of partner institution: MHRA-NIBSC
Abbreviation of partner institution: DH
Website of partner institution: www.nibsc.org/
Contact email of partner: mei.ho@nibsc.org

Description of partner institution

The National Institute for Biological Standards and Control (NIBSC) is a centre of Medicines and Healthcare Products Regulatory Agency (MHRA), an Agency of the UK Government’s Department of Health (DH). NIBSC’s mission is to play a major national and international role in assuring the quality of biological medicines through product testing, developing standards and reference materials, and carrying out applied research. NIBSC supports health policy development and implementation through provision of expert evidence-based advice and technical support, and are an important component of the Department of Health’s risk management strategy for public health. NIBSC is designated as the UK’s Official Medicines Control Laboratory for Biological Medicines, working closely with MHRA and operating within the European regulatory network to carry out independent official batch release testing of certain types of product as required by EU law. NIBSC is also the leading WHO International Laboratory for Biological Standards and a WHO collaborating centre. NIBSC occupies a unique international position at the interface between product manufacturers, regulators, policy makers and leading edge academic research. NIBSC serves a broad range of customers and stakeholders in the UK and abroad and has a worldwide reputation for independence, integrity and scientific excellence.

Role of partner institution in project

Our roles in the project include activities in WP4, 6, 17 and 19.

WP4, Task 4.5: The development of novel/ customised Luminex bead arrays will support the Luminex studies carried out in both the technology platform and the systems biology platforms.

WP6, Task 6.1 and 6.3: The investigation of predictive immunogenicity and efficacy of BCG vaccination will generate data from relevant models with a regimen comparable to human immunisation. Antigen specific lymphocyte responses and cytokine secretion profiles will be assessed by advanced flow cytometry. Innovative imaging technologies to monitor responses to vaccines and infections in suitable models will provide information in characterisation of live vaccine (such as BCG) of its biodistribution and persistence.

We will also contribute and support the activities in WP17 – Scientific-technical networking; and WP19, Task 19.2: Dissemination of project results to the scientific and corporate communities.

Name of main staff involved in the project

Dr. Mei Mei Ho

Dr. Bhagwati Khatri

A description of the Facility

NIBSC has a well-established, dedicated biological facility and relevant models for evaluating the protective potencies of BCG and new TB vaccine candidates. We are also equipped with advanced imaging system technology offering non-invasive longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in relevant models using non-virulent mycobacteria tagged with bioluminescense genes.

Our other facilities also provide Luminex and Meso Scale Discovery (MSD) platforms for the detection of cytokines and chemokines. Our Luminex 100 and 200 systems are based on the principles of flow cytometry. In a single reaction volume, Luminex has the ability to perform many different tests and use either magnetic beads or plain polystyrene beads. It has many applications including nucleic acid assays, receptor-ligand assays, immunoassays and enzymatic assays. MSD platform is based on the principles of ELISA with MULTISPOT panels for quantifying multiple analytes simultaneously from a single, small-volume sample. The assays are provided in a pre-coated 96- or 384-well microtiter plates. Biomolecules of interest are detected using SULFO-TAG– conjugated reporter molecules by MSD instruments.

PHE logo
Name of partner institution: Public Health England
Abbreviation of partner institution: PHE
Website of partner institution: www.gov.uk/government/organisations/public-health-england
Contact email of partner: cathy.rowe@phe.gov.uk

Description of partner institution

PHE is an executive agency of the UK Department of Health. The Microbiology Services Division at Porton Down, part of the National Infection Service directorate, has extensive high-containment laboratory facilities and rare capabilities to handle infectious organisms under the highest levels of containment, and the ability to work with in vivo models to evaluate new therapeutic interventions against these organisms. The research department has a significant number of translational research programmes involving the development of infectious disease vaccines, therapeutics and diagnostics. Many of these programmes are collaborations with the biotech/pharma sectors. The department has expertise in aerosol delivery of pathogens and therapeutics and in advanced imaging under high-containment conditions.

Role of partner institution in project

PHE is contributing to the “Animal models” platform with particular expertise in influenza and TB models. For influenza we offer the ferret model, the “gold standard” for infections with human influenza viruses, which will be used to assess the efficacy of vaccine candidates. PHE will provide scientific advice on vaccination approach and design, animal purchase and housing, biological sampling, all in vitro/in vivo work. In animal models joint research activity, PHE will contribute to studies in non-human primates where stored samples from BCG-vaccinated subjects (with a regimen comparable to human immunisation) will be used to generate data which will be comparable to humans. Antigen specific lymphocyte responses and cytokine secretion profiles will be assessed by advanced flow cytometry.

Name of main staff involved in the project

Cathy Rowe: general project manager

Miles Carroll: Deputy Director Head of Research

Bassam Hallis: project manager, influenza research

Anthony Marriott: project team leader, influenza research

Sally Sharpe: Scientific Leader for non-human primates and imaging.

Ann Rawkins: Scientific Leader for animal models and aerobiology

A description of the Facility

The PHE laboratories at Porton have high-containment laboratories and facilities for in vivo studies with BSL3 pathogens and expertise in the aerosol delivery of pathogens and therapeutics and advanced imaging under high containment. The facility comprises non-pathogenic and pathogen containment sections with 40 multi-species rooms that can be operated up to BSL3. The delivery of nose-only aerosols to mice, guinea pigs, ferrets and macaques and their subsequent housing in social groups is a unique capability. PHE owns on-site breeding colonies of rhesus and cynomolgus macaques. The department has expertise and infrastructure to support bacterial and viral analysis, and the detailed evaluation of cellular and serological immune responses including flow cytometry and cell sorting, Luminex multiplex platforms, real time PCR, microarrays, comprehensive histological staining, immunohistochemistry and in-situ hybridisation.

Services currently offered: We offer contract research based on the well-characterised animal models and infrastructure described above, which has been used in several EU projects. We carry out translational research programmes to develop infectious disease vaccines, therapeutics and diagnostics using animal models of tuberculosis, influenza, HIV/AIDS, Clostridium difficile, meningococcal disease, chlamydia, burkholderia and anthrax, as well as emerging viral diseases such as Crimean Congo haemorrhagic fever.

TNA/training that will be provided

PHE will provide access to the ferret model of influenza as part of TNA8 Animal models platform. Specifically, 1 unit of access comprising a vaccination/challenge study with 3 groups of 6 ferrets (control and 2 vaccine groups), to include vaccination/boost, intra-nasal challenge with influenza virus, monitoring of virus load (nasal washes), disease progression and immune responses (antibody, IFN gamma ELISA and ELISpot).

ITV logo
Name of partner institution: Institute for Translational Vaccinology
Abbreviation of partner institution: ITV
Website of partner institution: www.intravacc.nl
Contact email of partner: info@intravacc.nl

Description of partner institution

Intravacc is a renowned, not-for-profit translational R&D organization with 100+ years of experience in vaccine development.

We offer a wide range of solutions for optimizing vaccines, vaccine processes, and vaccine technologies. Our broad technological capabilities can guide your innovative vaccine concept through the development chain, bridging the gap between early discovery and late stage clinical studies.

We share and transfer our knowledge and technologies to partners worldwide, providing opportunities for contract research and out-licensing of (in-house) developed vaccine technologies.

Role of partner institution in project

ITV will provide access to its panel of neisserial LPS-derived adjuvant candidates. The service will include formulation, stability testing, physicochemical characterization of adjuvants and vaccines, and ex vivo innate response evaluation on cell lines or human antigen-presenting cells.

Name of main staff involved in the project

Dr. Peter van der Ley

A description of the Facility

Detoxified LPS immunomodulatory adjuvants are the most common PAMP compounds, but only one variant (from Salmonella) is currently included in a registered adjuvant product. Neisseria meningitidis contains a very potent hexa-acylated LPS that would be too toxic for therapeutic applications. We have used systematic molecular bioengineering of the meningococcal LPS through deletion of enzymes involved in LPS biosynthesis in combination with induction of LPS modifying enzymes (for example the deacylase PagL) to yield a variety of novel LPS mutant strains with changes in both lipid A acylation and phosphorylation. Altogether these purified LPS derivatives display a broad range of TLR4 activity and differential cytokine inducing properties, which can be exploited for use as an adjuvant in vaccines We will use our panel of genetically-detoxified LPS compounds to optimise their preferred presentation form and delivery vehicle. Their physicochemical states will be assessed, including aggregation behaviour and dynamics, and abilities to influence in vitro innate immune responses (antigen presenting cell (APC) activation, cytokine induction) quantified. The purified LPS will then be formulated in well-characterised particles, e.g. liposomes. The design space will be determined using parameters such as lipid composition, particle size, and LPS loading.

TNA/training that will be provided

Intravacc has several detoxified LPS variants available for testing with your antigen of choice. The LPS adjuvant platform technology of Intravacc is open for new collaborations, which can range from out-licensing to large collaborative development, process optimization and cGMP production.

CReSA logo IRTA logo
Name of partner institution: Institut de Recerca i Tecnologia Agroalimentàries
Abbreviation of partner institution: IRTA
Website of partner institution: www.cresa.cat and www.irta.cat
Contact email of partner: joaquim.segales@irta.cat

Description of partner institution

IRTA is a research institute owned by the Government of Catalonia (Spain) ascribed to the Department of Agriculture, Livestock, Fisheries and Food (DARP). IRTA's mission is to contribute to modernising, improving, boosting competitiveness, and fostering sustainable development in the sectors of agriculture, food, agroforestry, aquaculture, and fishing, as well as in all areas of activity directly or indirectly related to the supply of healthy, high-quality foodstuffs to end consumers, while also contributing to food safety and safe processing of foodstuffs and in general enhancing the health and well-being of the population. The animal health research program of IRTA is the Centre de Recerca en Sanitat Animal (CReSA), where Transvac2 activities will take place. CReSA activity is executed at the Edifici CReSA, which is a new and technologically advanced building, with conventional laboratories as well as biocontainment with level-3 biosafety (BSL-3) laboratories and animal facilities. The research at CReSA is being performed under the umbrella of three major activities: basic and applied independent research based on national and international projects (organized in 3 research subprograms: 1. Epidemiology and risk analysis, 2. Endemic diseases, and 3. Exotic or transboundary diseases), services for public administrations, and research contracts with agri-food sector companies.

Role of partner institution in project

IRTA is an institution that offers transnational access (TN8) to BSL3 facilities (including animal facilities, laboratory facilities or both) and its experience, acquired in a previous infrastructure projects and as a singular scientific-technical infrastructure (ICTS) of the Spanish government, will facilitate the accomplishment of its tasks in TRANSVAC2. IRTA-CReSA is an essential centre for vaccine development and efficacy testing, e.g. for African swine fever, classical swine fever, Haemophilus parasuis, bovine and caprine TB, Schmallenberg virus (SBV), Rift Valley fever virus (RVFV), avian influenza virus (including H5N1), and this expertise will be highly relevant to the consortium. IRTA has also developed multiple animal and/or arthropod models to work with zoonotic pathogens such as avian and swine influenza, RVFV, MERS-coronavirus, West Nile virus and chikungunya virus. Also, IRTA participates in joint research actions (JRA4), mainly on the area of comparative immunogenicity of vaccines between different model species and humans as well as immunization models for neonates. Finally, IRTA is involved in network activities (NA2, NA3 and NA4) within the so called scientific-technical networking, mainly on animal models, training programs in vaccinology and communication and dissemination of the results.

Name of main staff involved in the project

Joaquim Segalés, Virginia Aragón, Natàlia Majó, Xavier Abad, David Solanesy

A description of the Facility

CReSA counts with a biocontainment unit classified as BSL-3. The BSL-3 facility comprises about 1500 m2 of working spaces, devoted to laboratories (350 m2) and animal facility (1150 m2). In the laboratory area there are five fully equipped laboratories, for cell culture, virology, bacteriology, and molecular biology work. An additional laboratory is devoted to work with prions. In the animal facility area, there are eight boxes for large animals (pigs, ruminants) and two for poultry, one of them with four isolators. Two more rooms are dedicated to rodents and rabbits. A necropsy room is adjacent to the boxes. There are two more working spaces inside the biocontainment unit, 1500 m2 for air filtration (HEPA filtration) and 1500 m2 for the effluents treatment. This latter area includes 35 m2 for entomological studies that require using BSL-3 facilities. Outside of the biocontainment unit, CReSA has about 720 m2 of BSL-2 standard laboratories, fully equipped for works on molecular biology, pathology, virology, bacteriology, epidemiology, and entomology. All activities are carried out under the principles of good laboratory practices (GLP) and good clinical practices (GCP) quality regulation, confidentiality and following the European guidelines.

TNA/training that will be provided

IRTA offers expertise and facilities to internal and external clients (academic and industry) for fundamental and applied research on bacterial and viral vaccines, including expertise on pigs, poultry and ruminants in the fields of epidemiology, microbiology, virology, immunology, pathology, molecular biology, and entomology. We provide access to our BSL3 biocontainment facilities including flow cytometry and cell sorting in a BSL3 environment. Several animal models for translational research are available for immunogenicity and challenge studies: pigs (influenza viruses, Haemophilus parasuis, tuberculosis, torque teno viruses), goat (tuberculosis), sheep (Rift Valley fever), poultry (influenza), ferrets (influenza) and llamas (MERS-coronavirus). Animal models are also available for the most relevant infectious veterinary diseases in pigs, poultry and ruminants. IRTA can also provide scientific advice on the experimental design and methodology (including a report), all animal purchase, housing, maintenance and veterinary assistance, biological sampling, and immune monitoring by serology, cellular immunology (ELISpot, cell phenotyping), pathogen kinetics by classical and molecular methods in challenge studies, clinical chemistry and histology. IRTA can also provide training activities on the main areas of expertise depicted above, mainly in relation animal models.

Information to follow shortly

UNIL logo
Name of partner institution: Université de Lausanne
Abbreviation of partner institution: UNIL
Website of partner institution: www.unil.ch
Contact email of partner: roland.ventura@unil.ch

Description of partner institution

The Vaccine Formulation Laboratory (VFL) is based in the Department of Biochemistry at the University of Lausanne (UNIL). The department hosts 15 research groups and approximately 70 graduate students, and is a WHO Collaborating Centre in Immunology and Adjuvants. The wider university has over 13500 students and 2200 researchers.

The VFL was established by the World Health Organization in 2010, in order to allow the global vaccine community to gain open access to adjuvant technology and vaccine formulation expertise. Today UNIL-VFL provides access to adjuvants, adjuvant quality control technology, adjuvant formulation expertise, technology transfer, training, and bespoke adjuvant R&D services, allowing partners to gain optimal benefit from the use of adjuvants and vaccine formulation technology.

Role of partner institution in project

UNIL-VFL is leading the TRANSVAC2 work package 8 “Adjuvants and delivery systems service” which is the adjuvant and formulation platform of the consortium. This platform aims to provide users with access to adjuvants (suitable for pre-clinical use), access to customised vaccine formulation studies, and access to stability studies for adjuvanted vaccines. Furthermore, the work package activities will facilitate the development of characterised experimental vaccines suitable for further development and pre-clinical studies. As part of its work package 8 activities, UNIL-VFL is providing access to the expertise within its dedicated facility for adjuvant supply, vaccine formulation, and quality control of adjuvanted vaccines, so as to accelerate the optimisation and characterisation of stable and effective formulations. In addition, UNIL-VFL is participating in adjuvant R&D through work package 3.

Name of main staff involved in the project

Dr. Roland Ventura (Project Lead)

Dr. Livia Brunner (Scientific Lead)

A description of the Facility

UNIL-VFL provides access to adjuvants, adjuvant quality control technology, adjuvant formulation expertise, training, technology transfer, access to GMP adjuvants, and bespoke adjuvant R&D activities, allowing partners to gain optimal benefit from the use of adjuvants and vaccine formulation technology.

Adjuvants are increasingly used by the vaccine community and are essential components of modern vaccines, particularly for their ability to enhance and bias immune responses and for their dose-sparing properties. Often, the knowledge on how to access, down-select, and formulate adjuvants is not readily available to the majority of vaccine research groups. UNIL-VFL therefore acts as a resource for adjuvants and formulations with the following emphasis:

  • Formulation studies, including optimisation of adjuvanted vaccine candidates, stability studies, and the development of analytical methods to characterise antigen-adjuvant combinations
  • Preclinical evaluation of adjuvanted vaccine candidates, including a variety of quality control and stability study techniques
  • Technology transfer of methods, protocols, and procedures for the preparation and QC of adjuvants
  • Training on vaccine-adjuvant formulation and characterisation, through a variety of training types

TNA/training that will be provided

UNIL-VFL provides access to adjuvants that are either not covered by intellectual property rights or are readily negotiable under license agreements, including oil-in-water emulsions, water-in-oil emulsions, aluminium salts, liposome-based adjuvants, TLR agonists, microparticles, saponins, and combination adjuvants. Furthermore, UNIL-VFL provides access to a diverse range of formulation expertise and characterisation, quality control, and stability assays.

UNISI logo
Name of partner institution: University of Siena
Abbreviation of partner institution: UNISI
Website of partner institution: www.dbm.unisi.it/it
Contact email of partner: annalisa.ciabattini@unisi.it, santorof@unisi.it, Francesco.iannelli@unisi.it

Description of partner institution

The University of Siena, one of the oldest and first publicly funded universities in Italy founded in 1240, has about 2100 employees and a turnover of €400 million. The Department of Medical Biotechnology consists of many research groups covering biotechnology, vaccine development, infectious disease, immunopathology, microbiology, genetics and microbial immunity. The Laboratory of Molecular Microbiology and Biotechnology is part of this Department, and its research focuses on microbial genetics, host-pathogen interaction, recombinant vaccines and vaccine immunology.

Role of partner institution in project

UNISI is WP Leader of WP13 TNA7 “Immunocorrelates and Systems Biology”; and partner of WP5 JRA4 “Immuno-correlates and Systems Biology”, WP3 JRA1: Improved optimisation and harmonisation of cross-vector screening, WP7, TNA 1 “Cross-platform screening and optimisation service” and WP6 “JRA5: Animal models”

Name of main staff involved in the project

Gianni Pozzi, Prof., Donata Medaglini, Prof.; Francesco Iannelli, Prof., Annalisa Ciabattini, PhD; Elena Pettini, PhD, Fabio Fiorino, PhD, Francesco Santoro, MD, PhD, Alessia Donato, PhD student; Sara Sorgi, PhD student; Simone Lucchesi, PhD student.

A description of the Facility

UNISI has established a NGS platform based on Ion Proton instrument (Thermo Fisher) for targeted RNA sequencing. Laminar flow cabinets are present in a BLS2 area for RNA extraction from blood. For RNA quality and quantity assessment we have a Qubit fluorimeter and an Agilent Bioanalyzer.

Two advanced technologies for detecting and measuring multiple soluble biomarkers in soluble samples are also available in our facility, the Luminex xMap and flow cytometric CBA assay. Both systems can simultaneously detect many targets such as cytokines, chemokines and inflammatory biomarkers in a single sample that can be serum, plasma and tissue culture supernatants. Multiplexing analysis is especially useful when only a small amount of sample is available, maximizing the number of proteins that can be analysed. These technologies are particularly powerful when looking for changes in concentrations of multiple targets under specific conditions, such as following a vaccine administration, infection, or a drug treatment. The assays reduce sample requirements and time to results in comparison with traditional ELISA and Western blot techniques.

The laboratory has also all of the technologies required to produce recombinant bacteria expressing vaccine antigens to be used as non-pathogenic vaccine vectors. The laboratory has all of the technologies required to perform molecular work including gradient polymerase chain reaction (PCR) blocks, RT-PCR and FACS.

TNA/training that will be provided

UNISI provides expertise in the determination of transcriptomic profiles of blood samples using the Ion AmpliSeq™ Transcriptome Human Gene Expression Kit to prepare NGS libraries to be sequenced on the Ion Proton™ System. The expression level of 20,802 human genes is quantified by this approach, using as an input 10-100 ng of total RNA. The minimum guaranteed output is 8 million reads per sample.

UNISI provides expertise in the measurement of cell signalling proteins, such as cytokines, chemokines and inflammatory biomarkers in multiple samples (including serum, plasma and tissue culture supernatants), using a multiplex suspension array system or a flow cytometric bead assay. Both technologies allow the simultaneous detection of multiple factors in serum, plasma and tissue culture supernatants.

Moreover, UNISI produces recombinant bacteria expressing vaccine antigens to be used as non-pathogenic vaccine vectors. Services include the design and construction of new recombinant bacterial strains expressing requested proteins (i.e. vaccine antigens) and assessment of the surface expression of the protein by flow cytometric analysis.

UL logo
Name of partner institution: Leiden University
Abbreviation of partner institution: LU
Website of partner institution: www.universiteitleiden.nl and www.bmfl.nl
Contact email of partner: j.c.schoeman@lacdr.leidenuniv.nl and hankemeier@lacdr.leidenuniv.nl

Description of partner institution

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development. Despite major advances in medicine, many common diseases such as cancers, neurological or cardiovascular diseases, or auto-immune diseases, still lack effective treatments, or are still incurable. That is why our work to develop new and more effective drugs is essential. At the LACDR we work at the leading edge of drug-design and fundamental research of new drugs, optimisation of existing drugs, and personalised medicine.

See also: www.universiteitleiden.nl/en/science/drug-research

Role of partner institution in project

The BioMedical Metabolomics Facility Leiden (BMFL) offers a highly structured environment for advanced metabolomics studies. BMFL builds on fully validated, state-of-the-art platforms that each cover a part of the human metabolism and together span the complete human metabolome. In vitro and in vivo metabolomics is a powerful approach to characterise/evaluate the metabolic responses and changes occurring during immunisation and challenge studies.

Name of main staff involved in the project

Nelus Schoeman

Thomas Hankemeier

A description of the Facility

BMFL is the core facility of Leiden University and the Netherlands Metabolomics Centre (NMC) and its users include internal as well as external academic collaborators and pharmaceutical and industrial clients from all over the world, measuring over 15,000 profiles annually. BMFL does not only perform routine measurements, but operates at the frontier of metabolomics developments and opportunities. The BMFL team covers the complete track from involvement in experimental design, study set-up and sample collection to the actual measurements, data analysis, identification of unknown compounds and comprehensive feedback on the results. In close collaboration with partners, BMFL defines a tailor-made approach that offers the best fit between your biological question and optimal use of the potential of our highly advanced facilities.

TNA/training that will be provided

Modality of access under this proposal: Users will provide samples and together we will decide the relevant metabolic pathways to target and profile, based on the applicant’s biological question(s). Data analysis of metabolic profiles can be carried out by the users, or supported by the facility. Users can be trained at the facility if needed. Support offered under this TNA: Comprehensive targeted metabolomics profiling based on liquid chromatography – mass spectrometry. Platforms included: Lipid metabolism, Bile acids, Organic acids Central Carbon metabolism, Biogenic amines and amino acids, Acyl-carnitines, Eicosanoids, Endocannabinoids and oxidative stress markers. In agreement with the facility, users will decide the scope of the service, including which platforms are to be used.

Samples matrixes suitable for metabolomics analyses include in vitro: cell lysate and medium, and in vivo: Plasma, serum, urine, CSF, micro-dialysate and tissues

INRA logo
Name of partner institution: Institut national de la Recherche agronomique
Abbreviation of partner institution: INRA
Website of partner institution: INRA: www.inra.fr/en, VIM: www6.jouy.inra.fr/vim, PFIE: www6.val-de-loire.inra.fr/pfie_eng/
Contact email of partner: VIM: nicolas.bertho@inra.fr, PFIE: pierre.sarradin@inra.fr

Description of partner institution

Ranked the number one agricultural institute in Europe and number two in the world, INRA carries out mission-oriented research for high-quality and healthy foods, competitive and sustainable agriculture and a preserved and valorised environment. The INRA Animal health division contributes to Transvac2. Its main missions are to produce new knowledge and to contribute to coordination of research in the field of animal health and veterinary public health, a typical “one health” strategy.

Role of partner institution in project

All together INRA facilities power up (1) Research in multi-disciplinary domains through academic and industrial collaborations for the development of large animal models, therapeutics or new imaging devices, and (2) Training under several topics (biocontained experiments, introduction of new imaging methods for large animal models etc.), welcoming external teams which do not possess such an instrumental park for Transnational access.

Name of main staff involved in the project

Nicolas BERTHO, senior scientist, VIM

Isabelle SCHWARTZ-CORNIL, senior scientist, VIM

Sabine RIFAULT, head of VIM

Édouard GUITTON, study manager, PFIE

Céline BARC, study manager, PFIE

Mickaël RIOU, study manager, PFIE

Pierre SARRADIN, head of PFIE

A description of the Facility

Our research lab and an animal facility are contributing:

  • the VIM (Virology and Molecular Immunology) laboratory is located at the INRA centre of Jouy-en-Josas (close to Paris) and provides strong expertise in virology, biochemistry, immunology, vaccinology, dendritic cell biology, and genomics. Our expertise and infrastructure is sufficient to handle viral production and immunological analysis in BSL2 and BSL3 facilities. INRA-VIM has led several research projects on the vaccination of livestock (cattle, sheep and pigs) for bRSV, Bluetongue virus, influenza and Rift Valley virus.
  • the PFIE (Plateforme d’infectiologie experimentale) bio-contained animal facility, located in Nouzilly close to the city of Tours, is the largest and most versatile experimental facility in Infectiology in France. It is a livestock experimentation platform (50 permanent positions, 3500 m2 BSL3 and 2500 m2 BSL2 buildings and isolators for small species (mice and poultry)). PFIE works according to the certification ISO 9001 and is open to the whole research community, from either academic or private sectors, studying farm animal and zoonotic diseases, testing new diagnostic tools or vaccines against infectious diseases. INRA-PFIE participates in the H2020 INFRA VetBioNet.

TNA/training that will be provided

VIM carries out virology and immunology research using large animals such as pigs (influenza) and ruminants (RSV). We propose cytometer analysis using up to 20 different parameters, Fluorescent microscopy, in vitro restimulation cultures, qRT-PCR analysis, ELISA and ELISPOT. We produce live and inactivated viruses in our BSL2 and BSL3 facilities, and perform immunogenicity and efficacy studies in pigs (influenza) and sheep (RSV) with a focus on skin vaccination and extended monitoring of humoral and cellular immune responses in the blood and lung.

PFIE. All kind of projects using mice or farm animals can be performed, with most of animal and zoonotic pathogens up to BSL3.

PFIE can supply SPF mice, SPF poultry, germfree chicks (chicken and quails), health controlled pigs and small ruminants as well as cattle and ponies.

Various equipment is available in BSL3 containment like continuous telemetric monitoring of temperature in most species, fibro-, broncho- or laparoscopy for large and mid sized animals, ultrasonography, in vivo or ex vivo imaging in fluorescence and/or bio-luminescence: IVIS Spectrum® (Perkin Elmer) for small animals or organs, Cell Vizio® Dual Band confocal laser endomicroscopy (Mauna Kea Tech.), Fluobeam® (Fluoptics), surgery rooms, automated haematology and biochemistry analysers.

Instruct logo
Name of partner institution: Instruct Academic Services Limited
Abbreviation of partner institution: Instruct-ERIC
Website of partner institution: www.structuralbiology.eu
Contact email of partner: admin@structuralbiology.eu

Description of partner institution

Instruct-ERIC is a distributed European research infrastructure in structural biology, making high-end technologies and methods available to researchers.

Instruct infrastructure provides the technical frameworks with which we can interpret molecular and cellular functions. The main experimental technologies that Instruct offers are complementary, and increasingly link detailed atomic structure of single molecules or macromolecular complexes with their cellular context. Instruct offers access to the full catalogue of services in the infrastructure, through a single entry point. It supports proposals that use different technologies to build up knowledge of functional mechanisms and intracellular dynamics with atomic structure information and integrate these into an understanding of cellular processes in the native environment and in real time.

Role of partner institution in project

Through its centres Instruct-IT and Instruct-UK, Instruct-ERIC provides the expertise and the technology for performing specific structural biology studies that have a key role in vaccinology:

  • Structural analysis of vaccine antigens.
  • Engineering vaccines for improved physio-chemical properties.
  • Engineering vaccines for improved antigenic properties.

The users interested in structure characterisation and who wish to benefit from the Instruct-ERIC services will be guided so as to optimise their experimental planning and their application for Instruct-ERIC services.

Name of main staff involved in the project

Prof Lucia Banci (Instruct-IT) – NMR methods

Prof David Stuart (Instruct-UK) – X-ray methods

Prof Peijun Zhang (Instruct-UK) – cryo-EM methods

A description of the Facility

Instruct-ERIC provides its services via nine major Centres in Europe, and is coordinated from offices in Oxford, UK. The full catalogue of infrastructure services is described at www.structuralbiology.eu/platform-catalogue and the proposal management system is managed using the online tool ARIA. All access includes expert help and support for the user and the project. All data generated as part of the project remains the property of the user. Instruct Centres in Italy and the UK have special expertise in structural vaccinology and will provide the major services for TRANSVAC2 projects.

TNA/training that will be provided

The service provision model of Instruct-ERIC includes the close support, at all stages of the work, of expert scientists to ensure the best outcome for the researcher. If the user of access provision is onsite in an Instruct Centre, the supervision provides practical and theoretical training at source. In addition, Instruct hosts tailored practical training courses and workshops in advanced techniques and methods in structural determination which can be accessed by interested parties on a competitive basis. These courses and the upcoming programme of training events will be communicated to TRANSVAC participants.

Bioaster logo
Name of partner institution: BIOASTER
Abbreviation of partner institution: BIOASTER
Website of partner institution: www.bioaster.org
Contact email of partner: frederic.bequet@bioaster.org and corentin.chaboud@bioaster.org

Description of partner institution

BIOASTER is a non-for-profit technological research institute dedicated to applied microbiology created in 2012 by the French Government. BIOASTER conducts innovative collaborative research, with and for public and private partners in the four major application fields of microbiology including human and veterinary infectious diseases: vaccines, antimicrobials, diagnosis and microbiota.

Each applied research project, involving academics, SMEs and industrials partners, is undertaken by a team of high-level scientists and engineers integrating state-of-the-art technological equipment and expertise, dedicated to conceive and to develop new innovative and high value technology solutions.

With offices and laboratories in Lyon and Paris (2,500 m² laboratories including biosafety level 2 & 3 labs, BIOASTER has today more than 100 employees including 80 scientists and engineers originating from 16 different countries, involved in collaborative projects.

Role of partner institution in project

The Metabolomics & Proteomics Technology Unit will participate in the WP13 (TNA7) Immuno-correlates and Systems Biology work package of the project. BIOASTER will also participate in the Scientific-technical networking activities of the project.

Name of main staff involved in the project

Frédéric Béquet, PhD in Neurosciences. 12 years of expertise in metabolomics for drug discovery in the pharmaceutical industry and in the development of innovative analytical methods for biomarker analysis, with experience in metabolomics and imaging technologies coupling. Head of the Metabolomics & Proteomics Unit at BIOASTER.

Xavier Méniche, PhD in Biochemistry. Expertise in metabolomics and proteomics applied to microbiology, based on Mass Spectrometry approaches.

Kristin Hennig, PhD in Chemistry. Expertise in analytical chemistry, mass spectrometry and metabolomics.

A description of the Facility

The Metabolomics & Proteomics Technology Unit activity focuses on the identification of biomarkers and the functional characterization of metabolic pathways, applied to Research & Development of antimicrobials, vaccines, diagnostic tests or probiotics. The activity is based on approaches such as metabolic profiling, fingerprinting, fluxomics, quantitative metabolomics and MS Imaging. The unit is multidisciplinary and includes expertise covering all the value chain of metabolomics and proteomics, from automated sample preparation to data analysis and interpretation, including the development of innovative technologies and new analytical approaches.

TNA/training that will be provided

The Metabolomics & Proteomics Technology Unit will offer localizomics approaches based on Mass Spectrometry Imaging on tissue/organs slices (or on in-vitro cell cultures), either in targeted MS (e.g. drug and metabolites distribution) or in untargeted high resolution (HR) MS (metabolite profiling). The samples will be analysed on the MS Imaging platform by our qualified personal and the user will receive an image of the metabolite(s) of interest distribution. If needed, histology coloration can also be performed on the same tissue sample. For untargeted approaches, a list of relevant discriminant metabolites will be provided.

Applied training in Mass Spectrometry Imaging, based on the DESI technology, will also be proposed.

Board of Stakeholders

Non-executive advisory body to the infrastructure. Its role is to maximise on the European and international stages the integration, coordination and alignment of TRANSVAC2 with other related initiatives and with activities conducted by the vaccine R&D industry, to leverage the investments in TRANSVAC with other support mechanisms managed by other policy and decision makers, and to support the promotion of the long-term stability of a European vaccine R&D infrastructure.

SEAC

Non-executive body that provides expert scientific and technical advice and recommendations to the consortium. They undertake the continuous evaluation, revision and definition of the services offered by TRANSVAC2 to adjust services based on the evolution of technologies and methods, and according to the needs and demands of different target user groups. Also, SEAC members will review the scientific and experimental quality of all applications for TNA services received by the TRANSVAC2 infrastructure.

User Selection Panel

The USP is composed of reviewers with relevant expertise and experience in fields related to the TNA services offered. The USP assess the feasibility of submitted applications and recommends a short-list of the user applicants to access TNA services.

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