Services

Service overview

TRANSVAC2 offers a wide range of services, the majority of which can be accessed free-of-charge. These services range from shorter services lasting a few weeks, to longer services lasting several months. All of the available services and the institutions involved are summarised below.

Platforms

TRANSVAC’s services are organised in four different platforms: “Technology”, “Immunocorrelates and System Biology”, “Animal Models” and “Clinical Trial Support”. Applicants are encouraged to follow an integrated approach by apply for complementing services. Suggestions for complementing services are shown in the overview diagram and under the individual services.

Platform Technology

Description of service

Expression of vaccine antigens in plant-based systems. The Agrobacterium tumefaciens-based system is a robust platform to either rapidly produce up to mg-amounts of recombinant proteins or to compare larger numbers of different vaccine constructs in a screening approach preferentially by transient expression in N. benthamiana plants.

Dependent on the state of development and the focus of the corresponding project, the user may either request one of the following scenarios:

  1. the small scale expression of a larger number (up to 20) of constructs to compare yields, integrity in crude preparations.
  2. the small to medium scale expression (and purification) of a small number (up to 5) of constructs to compare yields, integrity and functionality.
  3. the medium scale expression of one defined vaccine antigen for further studies.

Or, may request a combination of the three performed in succession.

Affinity-tags will be used to facilitate easy purification and detection. Depending on the user projects future perspectives, the expression screening will include plant suspension cells and/or initiation of stable plant generation with respect to future manufacturing processes.

Related services

The service "Expression of vaccine antigens in plant-based systems" can be requested as a standalone service, or in the context of the "Cross-platform screening and optimization service" which enabled the user to have vaccine antigens expressed in several different platforms with the aim to compare yields, integrity and (if possible) functionality of the protein when produced in different systems. Once recombinant vaccine antigens produced by this service are available, they could be forwarded to Analytical services (TNA3), Adjuvants and delivery systems (TNA2) or Immunogenicity and efficacy studies (TNA8), if applicable. The work performed in the context of this service will also provide specifications and a starting point for the Pre-clinical GMP production (TNA4) services.

Publications related to service

‘A Plant-Based Transient Expression System for the Rapid Production of Malaria Vaccine Candidates’ (DOI: 10.1007/978-1-4939-3389-1_39)

‘Application of a Scalable Plant Transient Gene Expression Platform for Malaria Vaccine Development’ (DOI: 10.3389/fpls.2015.01169)

‘From Gene to Harvest: insights into upstream process development for the GMP production of a monoclonal antibody in transgenic tobacco plants’ (DOI: 10.1111/pbi.12438)

Possible output

Scenario a): Data on expression level, and integrity of the different variants. Recognition by user-supplied antigen-specific mAbs/or sera.

Scenario b): Data on expression level, and integrity of the different variants, Recognition by user-supplied antigen-specific mAbs/or sera, IMAC-purified proteins in the µg-range (in case of successful expression).

Scenario c): Data on expression level, and integrity of the different variants, Recognition by user-supplied antigen-specific mAbs/or sera, IMAC-purified proteins in the mg-range (in case of successful expression).

Sample requirements (Input of users)

There are different requirements for the different scenarios:

  1. Small scale expression of a larger number (up to 20) of constructs.
    Report featuring all relevant previous data on the vaccine antigen including data from recombinant expression performed by the user or co-workers. Definition of the AA-sequences. Synthetic genes encoding the desired protein sequences. Detection antibodies (if available).
  2. Small to medium scale expression (and purification) of a small number (up to 5) of constructs.
    Report featuring all relevant previous data on the vaccine antigen including data from recombinant expression performed by the user or co-workers. Definition of the AA-sequences. Synthetic genes encoding the desired protein sequences. Detection antibodies (if available). Specification of potential assays to address functionality (if applicable). Specification of requirements (purity, concentration, buffer composition) to perform functionality assays.
  3. Medium scale expression of one defined vaccine antigen.
    Report featuring all relevant previous data on the vaccine antigen including data from recombinant expression performed by the user or co-workers. Definition of the AA-sequences. Detection antibodies (if available). Specification of potential assays to address functionality (if applicable). Specification of requirements (purity, concentration, buffer composition) to perform functionality assays.

Services do NOT include

Costs for shipment of samples will be the responsibility of the User. Costs for synthetic genes will be covered only for one gene (Scenario C) for each user. In case several constructs or construct variants (Scenario A or B) need to be tested, the additional genes have to be supplied by the user.

Timelines

2-4 months depending on the complexity of the projects.

Unit of access

1 project

Capacity

9 units of access. One project at a time.

Provider

Frauenhofer Institute for Molecular Biology and Applied Ecology (IME), Achen, Germany. The IME Molecular Biology Division has a long standing expertise in the expression of recombinant proteins like therapeutic antibodies and vaccines using different transient and stable plant-based systems. These systems including transient expression in N.benthamina, and BY2 suspension cells, as well as stable expression in N.tabacum and BY2 suspension cells have been used successfully in many R&D projects primarily focusing on the expression on therapeutic molecules. In the context of the EU FP7 project Pharmaplanta the IME established a GMP-compliant process for the manufacturing of human HIV-specific mAb 2G12 in stable transgenic tobacco plants. A GMP-manufacturing process utilizing transient plant expression is currently under development.

Lead scientist

Holder Spiegel

Contact

Holger Spiegel, holger.spiegel@ime.fraunhofer.de, 0049241608512461

Description of service

Two different bacterial expression systems for recombinant protein production: E. coli and L. lactis. SSI will provide access to its E. coli and L. Lactis platforms and will discuss optimisations of the antigen sequence for the chosen platform, design of the expression cassette, and carry out test runs depending on the user's demands.

Related services

TNA2, TNA3, TNA5

Possible output

Initial cell clone and mg protein for testing.

Sample requirements (Input of users)

DNA sequence and characteristics of protein.

Services do NOT include

Access to expression system.

Timelines

3-5 months.

Unit of access

Expression in E. coli and/or L. lactis, in lab scale (mg scale).

Capacity

2-3 units of access. 2-3 projects per year.

Provider

The Statens Serum Institut (SSI), Vaccine Development Department (VUA) and Center of Vaccine Research (CVR), Copenhagen, Denmark, is internationally recognised for its vaccine research and clinical pipeline. This has yielded three TB vaccine candidates undergoing phase IIa testing and three first-in-human trials of novel CMI-inducing adjuvants. The department 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.

Lead scientist

Charlotte Green Jensen.

Contact

Charlotte Green Jensen, CGJ@ssi.dk, +45 32683963

Description of service

Small-scale mammalian and insect cells expression platforms. iBET will provide services related to mammalian and insect cell expression platform screening, and small-scale production and purification of candidate vaccines.

Related services

TNA2, TNA3, TNA8.

Possible output

Purified protein from small-scale mammalian and/or insect expression system.

Sample requirements (Input of users)

The user(s) shall contact iBET with at least 3 months lead time to define (1) service(s) to be provided by iBET, (2) expression system and process conditions to be used, (3) analytics to be performed, (4) (cost, in case of paid services) and timelines, and provide all other relevant information. Regular contacts per email and/or TCs shall be kept with the user(s) to inform about project progression.

Services do NOT include

Other services available at iBET that are NOT included in the free access:

  1. 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.
  2. GMP Mass-Spectroscopy Unit that provides state-of-the-art MS services to the scientific community and Industry.

Timelines

Timelines for the experiment(s): 2-16 weeks depending on the expression system (insect or mammalian cells) and method (transient or stable), with 3 months lead time.

Unit of access

Single protein expression.

Capacity

12 units of access. Maximum of two projects at once (capacity may be re-adjusted if needed).

Provider

iBET, Animal cell technology Unit and pilot scale facility of iBET, Oeiras, Portugal. 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 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 and has participated as a work package leader in more than 50 projects under EC FPs 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” from institutions within NOVA University of Lisbon.

Lead scientist

Paula Alves

Contact

Paula Alves, marques@ibet.pt, +351 21 446 94 21

Description of service

Protein Production: Pichia expression experiment (Small expression screen; scale up and purification of promising constructs)

Related services

TNA3 provides Analytics services of the protein(s) produced. TNA4 provides GMP production.

Possible output

Protein producing Pichia strain; Record of the full investigational process; data stored in electronic format; Product sheet with all relevant data (yield, purity etc.)

Sample requirements (Input of users)

Protein sequence to be produced.

Services do NOT include

Optimization producers are not included.

Timelines

A typical turnaround for the (successful) expression of proteins in Pichia, from (digital) sequence to pure protein (1-2 mg) would be 14 weeks.

Unit of access

‘Per protein’ production effort.

Capacity

Estimated total number of units: 15, 5 protein sequences can be processed in 1 round.

Provider

Foundation Biomedical Primate Research Centre (BPRC), the Netherlands. The department of parasitologyat BPRC has long-lasting experience with P. pastoris expression. A semi high-throughput screening system is available as well as small-scale production systems (3–7 L fermenters). The facility has produced a large variety of highly purified recombinant malarial proteins. Some of the clones were used to derive GMP cell banks suitable for GMP production and human vaccine testing. Additional recombinant proteins were produced from dengue virus, humans, macaque and marmoset monkeys.

Lead scientist

Bart Faber

Contact

Bart Faber, Faber@bprc.nl, +31 15 284 2516

A cross-platform expression screening of some/all the four expression services described above.

Description of service

Viral Vectored vaccines, Adenovirus (human and chimpanzee) and MVA. Jenner Institute's Viral Vecor Core Facility (VVCF) will produce Adenovirus and/or MVA vector(s) expressing antigen(s) of interest to the accessor, with appropriate QC. Vector design, for example insert size, expression of multiple antigens, inclusion of a signal sequence and Adenovirus backbone, will be discussed. When required, both Ad and MVA vectors expressing the same antigen(s) can be produced, to enable prime-boost vaccination strategies. Several different Ad backbones are available (human/primate).

Possible output

Ad or MVA viral vector vaccines, frozen in aliquots, and QC data: titre (viral particles/infectious units for Ad, pfu for MVA), sterility and identity/purity assessed by PCR. 10^8pfu (MVA), 10^10vp (Ad).

Sample requirements (Input of users)

DNA encoding the antigen(s), and DNA sequence data. Function of the antigen and potential pathogenicity. Prior experience expressing antigen, e.g. relevant publications. Any other relevant information e.g. expressed as trimer, is secreted/has transmembrane domain, is glycosylated.

Services do NOT include

Additional QC e.g. sequencing and mycoplasma.

Timelines

6 weeks for Ad vector, 8 weeks for MVA. Starting date to be discussed with user (depends on number of users accessing this service simultaneously).

Unit of access

1 viral vectored vaccine, either Adenovirus or MVA.

Capacity

40 units of access (15 non-GLP and 5 non-GLP but GMP-compliant MVA (108pfu) and 15 non-GLP and 5 non-GLP but GMP-compliant Adeno vectors (1010vp)). Several projects can be run simultaneously.

Provider

University of Oxford (UOXF), Jenner Institute's Viral Vecor Core Facility (VVCF), UK. The facility routinely produces human and primate Adenovirus (Ad) and MVA vectors for pre-clinical testing. Virus-vectored vaccines are produced at high yields with appropriate QC, and are suitable for antigen screening in animal models. Services include the construction of new recombinant viral vectors. QC includes virus titration, confirmation of identity, and sterility.

Lead scientist

Professor Adrian Hill

Contact

Dr Ali Turner, ali.turner@ndm.ox.ac.uk, +44 (0)1865 287761

Description of service

UNISI will provide access to the design and construction of commensal bacterial strains displaying selected antigens on their surface. S. gordonii is a human commensal bacterium which has been developed to deliver mucosal vaccines. A genetic system for stable chromosomal integration allows the expression of recombinant proteins on the bacterial surface. This system also allows the co-expression of two heterologous molecules on the surface of the same bacterial vector, i.e. vaccine antigens and adjuvant molecules or two different vaccine antigens.

Publications related to service

  1. Pozzi G et al. Delivery and expression of a heterologous antigen on the surface of streptococci. Infect Immun. 1992 May;60(5):1902-7
  2. Oggioni MR et al. Engineering the gram-positive cell surface for construction of bacterial vaccine vectors. Methods. 1999 Sep;19(1):163-73. Review
  3. Oggioni MR, Pozzi G.A host-vector system for heterologous gene expression in Streptococcus gordonii.Gene. 1996 Feb 22;169(1):85-90

Possible output

The recombinant strain, together with analysis of protein expression (i.e. western blot, or dot plot, or FACS analysis).

Sample requirements (Input of users)

The sequence of the protein to express on the recombinant strain.

Timelines

Three months from receiving the sequence.

Unit of access

One recombinant bacterial strain expressing a heterologous antigen.

Capacity

Three units of access.

Provider

UNISI-DBM. The laboratory of molecular microbiology and biotechnology (LAMMB, part of the department of medical biotechnology) focuses its research on bacterial genetics, recombinant vaccines and mucosal immunology, microbial pathogenicity, and clinical microbiology. A host-vector system has been developed that allows the genetic manipulation of Gram+ bacteria surface expression or secretion of heterologous antigens in Streptococcus gordonii and other Gram+ bacteria. By using this system, a variety of antigens, of different origin and size, have been expressed on the surface of S. gordonii. The laboratory has all of the technologies required to perform molecular work including gradient polymerase chain reaction (PCR) blocks, RT-PCR and FACS.

Lead scientist

Gianni Pozzi.

Contact

Francesco Lannelli, francesco.iannelli@unisi.it, 0039-(0)577-233156

Description of service

Users can ship their antigens to the VFL for formulation with one of a variety of the VFL’s adjuvants (the VFL has a wide range and grade of adjuvants available within its portfolio). Users can request a specific adjuvant or ask the VFL for recommendations or advice. Antigens will be optimally formulated with the selected adjuvant(s) and in vitro characterisation and short-term stability studies performed. If required and feasible, antigen characterisation may also be performed. Training can also be provided in certain circumstances. A summary of the results of the formulation/stability studies obtained with each formulation will be provided to the user.

Possible output

Summary of results.

Sample requirements (Input of users)

Various. To be discussed before starting

Services do NOT include

No in vivo studies or longer term stability studies.

Timelines

Project duration approximately two months.

Unit of access

One formulation.

Capacity

38 units of access. Capacity to carry out multiple projects is possible.

Provider

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:

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

Lead scientist

Dr. Livia Brunner

Contact

Dr. Roland Ventura, roland.ventura@unil.ch, +4915775722211

Description of service

SSI will formulate the candidate antigens with their cationic liposomal adjuvant systems CAF01 or CAF09b. Short-term stability testing of the CAF-adjuvanted vaccines and physicochemical characterisation of the vaccines will be carried out. SSI will supply with preclinical grade CAF01 and CAF09b for Efficacy studies in diverse animal models. SSI will advise on the formulation of the antigen with the adjuvant and the design of immunogenicity experiment.

Related services

TNA4: Pre-clinical GLP production services, TNA8: Animal models.

Publications related to service

http://www.sciencedirect.com/science/article/pii/S0264410X14007269?via%3Dihub

http://www.nature.com/articles/srep19570

Possible output

Optimised vaccine formulation and characterisation data. Access to T cell inducing adjuvants (accessible for further development in GLP and GMP quality) for proof-of- efficacy and/or immunogenicity of own antigens.

Sample requirements (Input of users)

The user must provide vaccine antigen ready to formulate with adjuvant, either lyophilised or in stable aqueous solution including documentation of physico-chemical properties and analytical methods to detect, quantify and characterise the antigen.

Services do NOT include

In vivo testing of formulation is NOT included. Formulation and characterization of vaccine as well as in-vivo testing is NOT included.

Timelines

Approx. 8-12 weeks per project.

Unit of access

Vaccine formulation with CAF01 or CAF09b adjuvant. Access to CAF01 and CAF09b for preclinical studies.

Capacity

6-8 formulations, up to 4 projects. 40 batches of up to 100 doses. 2 projects at a time.

Provider

The Statens Serum Institut (SSI), Vaccine Development Department (VUA) and Center of Vaccine Research (CVR), Copenhagen, Denmark, is internationally recognised for its vaccine research and clinical pipeline. This has yielded three TB vaccine candidates undergoing phase IIa testing and three first-in-human trials of novel CMI-inducing adjuvants. The department 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. Department of Infectious Disease Immunology is internationally recognised for its vaccine research and clinical pipeline. This has yielded three TB vaccine candidates undergoing phase IIa testing and three first-in-human trials of novel CMI-inducing adjuvants.

Lead scientist

Ida Svahn Rasmussen, Dennis Christensen

Contact

Ida Svahn Rasmussen, idsr@ssi.dk, +45 32683943

Dennis Christensen, den@ssi.dk, +45 32683804

Description of service

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 and formulation, including mucosal adjuvants. Within the framework of TRANSVAC2, the HZI will offer access in the form of pre-clinical studies in the murine system to assess the immunogenicity, safety and efficacy of specific vaccine formulations containing a mucosal adjuvant. The access includes animal breeding, housing, caretaking and biotechnical expertise for mouse studies on a vaccine candidate including sampling and standard immune monitoring to carry out validation experiments for potential users. Each unit of access will correspond to one formulation, i.e. a combination of one antigen (provided by the user) with one adjuvant from the HZI portfolio of mucosal adjuvants (e.g. STING agonists such as c-di-AMP, TLR2/6 agonist) or combination adjuvants, followed by extensive in vitro and in vivo characterization. A summary of the results obtained with each formulation will be provided to the user. More specifically, access will comprise: (i) the purchase and/or breeding of animals, including housing and animal care; (ii) support in the area of vaccinology to advise on the experimental design, vaccination protocol and methodology for the immune monitoring; (iii) conduction of immunizations and subsequent monitoring for the appearance of acute side effects; (iv) the sampling of blood and/or organs for the characterization of the immunogenicity of the corresponding formulation; (v) performance of standard tests to characterize antigen-specific humoral and cellular immune responses at both systemic and mucosal territories (e.g. total antibodies and IgG subclasses in sera, secretory IgA, Th responses, CTL, Elispots, cytokines, etc.); (vi) documentation of results for all experiments conducted during the project; (vii) access to raw data; (viii) appropriate conservation and storing of biological samples, if required; (ix) data analysis in collaboration with external users; and (x) advice and support for legal and ethical requirements, including preparation of applications for animal studies.

Related services

TNA 8 (Animal models - animal validation platform).

Possible output

A summary of the results obtained with each formulation will be provided.

Sample requirements (Input of users)

Material (e.g. vaccine and vaccine positive control) suitable for preclinical in vivo immunisation studies will be provided by the user.

Services do NOT include

Vaccine/antigen production.

Timelines

Approximately 10-12 weeks (experiment duration). This might be affected by the experimental conditions (e.g. evaluation of memory responses).

Unit of access

1x Formulation.

Capacity

6 units of access. A max. of 2 projects at once.

Provider

Helmholtz Centre for Infection Research (HZI), Mucosal adjuvant platform, Germany. 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 the 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. In order 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). The HZI carries out research into infectious diseases, investigating the mechanisms of pathogenesis to develop new strategies for prevention, diagnosis and therapy. The team at the HZI providing access through the project has access to state-of-the-art laboratories and animal facilities with BSL2 containment, flow cytometry and cell sorting facilities, histopathology and in vivo imaging (IVIS). The HZI animal facilities accommodate ~20.000 mice and provide containment up to BSL3.

Lead scientist

Carlos A. Guzman, MD PhD

Contact

Carlos A. Guzman, MD PhD, carlos.guzman@helmholtz-hzi.de, +49 531 6181 4600

Description of service

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.

Publications related to service

http://www.nature.com/articles/srep36575

Sample requirements (Input of users)

Antigens of sufficient purity to make addition of LPS adjuvants meaningful

Services do NOT include

Animal immunisation experiments.

Timelines

Earliest start date October 2017.

Unit of access

One formulation of antigen in LPS adjuvant.

Capacity

4-8 units of access. 2 users/2 projects at the same time.

Provider

Institute for Translational Vaccinology (Intravacc), Netherlands, is a renowned, not-for-profit translational R&D organization with 100+ years of experience in vaccine development. ITV will provide access to its panel of neisserial LPS-derived adjuvant candidates. 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.

Lead scientist

Dr Peter van der Ley

Contact

Dr Peter van der Ley, peter.van.der.ley@intravacc.nl, +31-30-7920477.

Description of service

Analytical services "Structural Integrity". Set of basic assays to address a vaccine candidate antigens size, purity, quantity assembly status (multimers and/or aggregates), and integrity using analytical PAGE, SEC, FPLC/HPLC methods.

Related services

The results obtained by this service may be part of the documentation provided to other analytical services (TNA3), Adjuvants and delivery systems (TNA2) or Immunogenicity and efficacy studies (TNA8) as well as the Pre-clinical GLP production services (TNA4) and the GMP production services (TNA5).

Publications related to service

"Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits.“ (DOI: 10.1111/pbi.12255)

“Production, Quality Control, Stability and Pharmacotoxicity of a Malaria Vaccine Comprising Three Highly Similar PfAMA1 Protein Molecules to Overcome Antigenic Variation” (DOI:10.1371/journal.pone.0164053)

Possible output

Report summarizing the results obtained in the different assays regarding protein a) purity, b) size, c) integrity, d) assembly status, and quantity.

Sample requirements (Input of users)

Purified protein samples either in solution or lyophilized/freeze-dried. High concentrations are helpful (1mg/ml). Minimum amount for complete comprehensive analysis 500µ-1mg.Sequences, biophysical properties, storage buffer compositions and further available information on stability.

Services do NOT include

Costs for shipment of samples will be the responsibility of the User.

Timelines

2 months.

Unit of access

Analysis of one protein or up to four related variants of a given protein.

Capacity

9 units of access. Max. 3 per year, one project at a time.

Provider

Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany. The IME Molecular Biology Division has a long standing expertise in the expression of recombinant proteins like therapeutic antibodies and vaccines using different expression platforms. Besides bench, and production-scale up-, and downstream capacities a full range of analytical methods and instruments is available, ranging from analytical SEC, FPLC, HPLC, and different spectroscopic methods towards molecular interaction analysis by SPR.

Lead scientist

Holger Spiegel.

Contact

Holger Spiegel, holger.spiegel@ime.fraunhofer.de, 0049241608512461.

Description of service

SPR-based molecular interaction analysis. In the context of this service IME will develop and perform assays that can be used to either:

  1. Characterize the interaction between biomolecules (e.g. protein and natural ligand, protein and conformational mAb) on quantitative and qualitative level.
  2. Characterize, and quantify antibody responses in serum samples (before, during or after immunization studies).

In the context of vaccine development and vaccine manufacturing these assays can provide a high value. Using so called calibration-free concentration analysis (CFCA) it is usually possible to address the total concentration of vaccine antigen specific antibodies in serum samples. Analysis interaction of vaccine antigens with natural ligand or antibodies can be used to investigate the activity and homogeneity of the protein and can be implemented during vaccine candidate development, process development and quality control.

Related services

This service could be utilized to analyse samples derived in the context of other services offered by TRANSVAC2, including the recombinant vaccine antigens provided by the "Cross platform screening and optimization service", the "Pre-clinical GLP production service" or even the "GMP production service". Furthermore serum samples or immune Ig preparations generated in the context of immunogenicity and challenge studies performed under the umbrella of the "Animal Models" could be analysed.

Publications related to service

"Analysis of a multi-component multi-stage malaria vaccine candidate-tackling the cocktail challenge" (DOI: 10.1371/journal.pone.0131456)

“Immunization with the Malaria Diversity-Covering Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 DiCo in Complex with Its Natural Ligand PfRon2 Does Not Improve the In Vitro Efficacy“ (DOI: 10.3389/fimmu.2017.00743)

"Detailed functional characterization of glycosylated and nonglycosylated variants of malaria vaccine candidate PfAMA1 produced in Nicotiana benthamiana and analysis of growth inhibitory responses in rabbits.“ (DOI: 10.1111/pbi.12255)

Possible output

Depending on the character of the analysis:

  1. Absolute or relative binding activities
  2. Thermodynamic interaction constants (kon, koff, KD, ΔH and ΔS)
  3. Stoichiometry of interaction
  4. Absolute concentrations of antigen specific antibodies
  5. Other parameters

Sample requirements (Input of users)

The specification of sample requirements will vary from project to project.

In general recombinant protein samples should have a high degree of purity (>75%).

High concentrations are helpful (1mg/ml). The minimum amounts strongly depend on the stoichiometry of the interaction, the affinity of the interaction as well as the molecular weights of the interaction partners. As a rule of thumb at least 100µg of the interaction partners should be available.

Sequences, biophysical properties, buffer compositions and further information on the ligands have to be provided by the user, together with a documentation demonstrating the state of purity and integrity (if applicable).

For the characterization of immune Ig, purified antibody preparations (e.g. Protein G or Protein A) are preferred. In case of human sera special requirements may apply.

Services do NOT include

Costs for shipment of samples will be the responsibility of the User. Recombinant proteins required as interaction partner (apart from standard capture ligands like protein A/G/L or human, mouse or rabbit antibody specific ligands).

Timelines

Upon the availability of all required samples and reagents, simple analytical tasks can be completed within 2-4 weeks. Modification of existing or development of new assay formats may require 4-6 weeks.

Unit of access

Addressing a specific analytical question.

Capacity

9 units of access. 5-10 per year depending on the complexity of the projects. One project at a time.

Provider

Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany. The IME Molecular Biology Division is internationally recognised for its expertise in the provision of state-of-the-art label-free assays for protein interactions based on SPR spectroscopy using different state of the art instruments.

Lead scientist

Holger Spiegel.

Contact

Holger Spiegel, holger.spiegel@ime.fraunhofer.de, 0049241608512461.

Description of service

Luminex potency assay for cytokine/chemokine responses in human blood. 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.

Publications related to service

  1. Smith SG et al. Broad heparin-binding haemagglutinin-specific cytokine and chemokine response in infants following Mycobacterium bovis BCG vaccination. Eur J Immunol. 2012 Sep;42(9):2511-22
  2. Lalor MK et al. BCG vaccination induces different cytokine profiles following infant BCG vaccination in the UK and Malawi. J Infect Dis. 2011 Oct 1;204(7):1075-85

Possible output

Raw data will be provided to users in the form of cytokine concentrations measured in potency assay samples.

Sample requirements (Input of users)

Users should provide vaccine formulations in sufficient quantities for testing in between 5 and 10 donor blood samples.

Services do NOT include

Shipment of vaccine formulations. Travel/accommodation/other costs of users who access the facility for the purposes of training etc.

Timelines

Earliest access to the service will be January 2019. Once initiated, projects will run for approximately 1-2 months once vaccine formulations are received.

Unit of access

One unit of access is defined as a single Luminex assay plate (accommodating approximately 78 samples).

Capacity

20 Units (i.e. 20 luminex assay plates) will be provided. Estimated 5 users at 4 plates each. Capacity to only process one project at a time.

Provider

London School of Hygiene and Tropical Medicine. 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.

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.

Lead scientist

Dr. Steven Smith.

Contact

Dr. Steven Smith, steven.smith@lshtm.ac.uk, (+44) 207 927 2295.

Description of service

ICS (Intracellular Cytokine Staining).

Related services

ICS analysis, mass cytometry analysis, in vivo imaging, methodology and statistical consultancy, flow and mass cytometry courses, in vivo imaging courses.

Publications related to service

www.ncbi.nlm.nih.gov/pubmed/23184609

Possible output

FCS files, single sample analysis and simple global overview of the results.

Sample requirements (Input of users)

Cells (frozen or fresh PBMC) and antigens to be tested with specification datasheets.

Services do NOT include

Integration of the analysis with other datasets.

Timelines

Two weeks provided all the reagents are available (cells, antigens and antibodies).

Unit of access

One staining.

Capacity

300 units of access.

Provider

CEA-IDMIT, France.

Lead scientist

Antonio Cosma.

Contact

Antonio Cosma, antonio.cosma@cea.fr, +33(1)46548757.

Currently not available. Information to follow shortly.

Description of service

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. The combined use of the aforementioned cell-line based assays in a tiered testing strategy provides rapid, detailed, robust and quantitative information about the innate immune responses that are induced by vaccines, adjuvants or components thereof, resulting in innate immune response fingerprints.

Related services

TNA1 provides protein expression systems.

Possible output

Users will receive all raw data as well as a report (pdf) containing a detailed analysis of the data.

Sample requirements (Input of users)

Samples should be provided for in sufficiently concentrated stock and be compatible with cell culture (i.e. in vitro analysis).

Services do NOT include

Sample shipment.

Timelines

Experiments will take approximately 1 year from start to finish.

Unit of access

1 Formulation/compound or a small series (maximum 10) of related formulations/compounds. Per formulation/compound analysis of innate immune profile.

Capacity

Full analysis of up to 3 formulations/compounds is provided for. Multiple projects can be executed in parallel.

Provider

Foundation Biomedical Primate Research Centre (BPRC), the Netherlands. Biomedical Primate Research Centre (BPRC) is the largest European biomedical primate research facility and has a long and successful collaborative track record with institutions in Europe and elsewhere. BPRC applies molecular, biochemical and immunological know-how to provide new vaccine and therapeutic strategies for malaria, tuberculosis, HIV, hepatitis C and other infectious diseases. BPRC has considerable experience in preclinical vaccine development, has played a leading role in taking malaria vaccines to the clinic, and in establishing comparative assay systems for malaria and other vaccines. BPRC also has an active programme to develop alternatives for animal experiments following the ethical principles of reduction, refinement and replacement (3Rs).

Lead scientist

Jeffrey Bajramovic.

Contact

Jeffrey Bajramovic, bajramovic@bprc.nl, +31 284 2722.

Currently not available. Information to follow shortly.

Description of service

Access to a GLP production platform suited for production of recombinant vaccine candidates in multi-mg range. SSI offers a GMP-directed evaluation of the user's vaccine candidate production process. SSI will be able to scale up bench scale production processes to achieve sufficient amounts of vaccine for the following tasks: characterisation, verification of proof-of-principle data, toxicity studies and development of robust assays.

Related services

TNA 2: Adjuvation.

TNA 5: GMP-production.

TNA 8: Animal models.

Possible output

A report on the technical, economical and regulatory aspects of an existing bench-scale process. Drug substance up to the multi-mg range. Drug substance and/or drug product specification. Drug substance formulation development report. Formal stability study, according to the relevant guidelines. Detailed development status including a list of action points to complete the IMPD. Preclinical material generated in a “comparable” process.

Sample requirements (Input of users)

The user must provide a described bench-scale process and culture stabs to start up the GLP-production.

Services do NOT include

Fill and finish and training is not included.

Timelines

Typical projects will last 3–12 months, depending on the maturity of the customer’s process.

Unit of access

1 project.

Capacity

2 units of access. 2 GLP-projects per year.

Provider

Vaccine Development Department (VUA), Center of Vaccine Research (CVR), Statens Serum Institut (SSI), Copenhagen, Denmark. The Statens Serum Institut (SSI) Department of Vaccine Development is internationally recognised for its vaccine research and clinical pipeline. This has yielded three TB vaccine candidates undergoing phase IIa testing and three first-in-human trials of novel CMI-inducing adjuvants. The department 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.

Lead scientist

Anders Bæk Vestermark.

Contact

Anders Bæk Vestermark, abv@ssi.dk, +45 32683853.

Description of service

Infrastructure in its non-GMP development laboratories and pilot scale facility for technical runs and production of preclinical material. iBET will be involved in activities related with 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, and evaluation of development, manufacturing and finishing documentation.

Possible output

Maximum of 12 products shall be produced and provided to the user.

Sample requirements (Input of users)

The user(s) shall contact iBET with at least 3 months lead time to define (1) service(s) to be provided by iBET, (2) expression system and process conditions to be used, (3) analytics to be performed, (4) cost and timelines, and provide all other relevant information. Regular contacts per email and/or TCs shall be kept with the user(s) to inform about project progression.

Services do NOT include

Other services available at iBET that are NOT included in the free access:

  1. 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.
  2. GMP Mass-Spectroscopy Unit that provides state-of-the-art MS services to the scientific community and Industry.

Timelines

Timelines for the experiment(s): 2-16 weeks depending on the expression system (insect or mammalian cells) and method (transient or stable).

Date when the service will be available: From M1 to M42, with 3 months lead time (4UA in first year).

Unit of access

GLP production.

Capacity

Maximum of two projects at once (capacity may be re-adjusted if needed).

Provider

iBET, Oeiras, Portugal, 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 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 and has participated as a work package leader in more than 50 projects under EC FPs 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” from institutions within NOVA University of Lisbon.

Lead scientist

Paula Alves.

Contact

Paula Alves, marques@ibet.pt, +351 21 446 94 21.

Description of service

This TNA is for production of GMP compliant starting material. The VVCF will produce Adenovirus and/or MVA vector(s) expressing antigen(s) of interest to the accessor, with appropriate QC. Vector design, for example insert size, expression of multiple antigens, inclusion of a signal sequence and Adenovirus backbone, will be discussed. When required, both Ad and MVA vectors expressing the same antigen(s) can be produced, to enable prime-boost vaccination strategies. Several different Ad backbones are available (human/primate).

Possible output

To be discussed with user: For MVA, markerless virus potentially suitable for transfer to GMP manufacturing organisation (frozen in aliquots, with QC data: titre in pfu, sterility and identity/purity assessed by PCR). For Ad, virus or DNA (whole genome plasmid) which could be used to prepare pre-GMP starting material.

Sample requirements (Input of users)

DNA encoding the antigen(s), and DNA sequence data. Function of the antigen and potential pathogenicity. Prior experience expressing antigen, e.g. relevant publications. Any other relevant information e.g. expressed as trimer, is secreted/has transmembrane domain, is glycosylated.

Services do NOT include

Additional QC e.g. sequencing and mycoplasma. Preparation of GMP starting material (to be discussed with user).

Timelines

1 viral vectored vaccine (GMP compliant), either Adenovirus or MVA.

Unit of access

10^8pfu (MVA) 10^10vp (Ad).

Capacity

5 MVA and 5 Adeno vectors. Several projects can be run simultaneously.

Provider

University of Oxford (UOXF), Jenner Institute's Viral Vecor Core Facility (VVCF), UK. The facility routinely produces human and primate Adenovirus (Ad) and MVA vectors for pre-clinical testing. Virus-vectored vaccines are produced at high yields with appropriate QC, and are suitable for antigen screening in animal models. Services include the construction of new recombinant viral vectors. QC includes virus titration, confirmation of identity, and sterility.

Lead scientist

Professor Adrian Hill.

Contact

Dr Ali Turner, ali.turner@ndm.ox.ac.uk, +44 (0)1865 287761.

Description of service

GMP production of recombinant vaccine candidates for clinical trials phase I/II. SSI offers Manufacture of GMP master/working cell banks and manufacture of clinical-grade vaccine candidate (drug substance).

Related services

TNA1, TNA2, TNA3.

Possible output

A GMP documented and QA released antigen to be used in vaccine formulation.

Sample requirements (Input of users)

Aminoacid sequence and requirements for antigen characteristics, (folding, size, aggregation).

Services do NOT include

Fill and finish.

Timelines

12 months.

Unit of access

1 GMP project.

Capacity

3 GMP projects per year.

Provider

Vaccine Development Department, Statens Serum Institut. GMP Pilot plant facility, Copenhagen, Denmark. The Statens Serum Institut (SSI) Department of Vaccine Development is internationally recognised for its vaccine research and clinical pipeline. This has yielded three TB vaccine candidates undergoing phase IIa testing and three first-in-human trials of novel CMI-inducing adjuvants. The department 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.

Lead scientist

Charlotte Green Jensen.

Contact

Ingrid Kromann, IKR@ssi.dk, +45 32688252.

Currently not available. Information to follow shortly.

Description of service

GMP production services, pay-per-service basis.

Publications related to service

http://www.genibet.com/

Possible output

GMP Master and Working Cell Banks; GMP Master and Working Virus Seed Stocks; GMP batches released by QP to be used in Clinical Trials.

Sample requirements (Input of users)

Project dependent.

Services do NOT include

Pay-per-service bases. Conditions to be agreed in a case by case.

Timelines

Case dependent.

Capacity

GenIbet has 3 independent production units that can work simultaneously.

Provider

GenIbet Biopharmaceuticals, Portugal. 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

Lead scientist

Tiago Ferreira.

Contact

Tiago Ferreira, tiago.ferreira@genibet.com, + 351214469484.

Description of service

Beamline IO3. The diamond synchrotron facility offers, through Instruct, the IO3 tuneable X-ray beamline for macromolecular crystallography which uses automated sample changing and plate technology. Capabilities include handling samples in Hazard Groups 2 and 3. In situ data collection and automated data analysis is available and data can be retrieved at the synchrotron or remotely after a visit. Guidance is available at the beamline.

Possible output

Experimental data collected at the beamline is stored locally and made available to access for 40days. Data analysis can be done onsite while at the beamline. Further refinement tools are available for structure analysis.

Sample requirements (Input of users)

Information to follow shortly.

Services do NOT include

Post collection structure refinement.

Timelines

Information to follow shortly.

Unit of access

On demand.

Capacity

8h shift. Multiple samples possible.

Provider

Instruct, UOXF/DIAMOND, UK. Instruct-ERIC is a distributed research infrastructure in structural biology, making high-end technologies and methods available to researchers. Instruct-ERIC provides the technical frameworks with which we can interpret molecular and cellular functions. The main experimental technologies that Instruct-ERIC offers are complementary, and increasingly link detailed atomic structure of single molecules or macromolecular complexes with their cellular context. Instruct-ERIC 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.

Lead scientist

David Stuart.

Contact

Martin Walsh, martin.walsh@diamond.ac.uk, 44 1235778518.

Description of service

CERM/CIRMMP offers access to state of the art NMR instrumentation and expertise to perform, at the highest level, the most comprehensive array of experiments needed for the structure and dynamic characterization of biological macromolecules and their complexes in solution and at solid state. Guidance is available on sample preparation ahead of the use of high-field spectrometers and for data collection.

Possible output

Raw data, processed data and guidance for data processing. Data processing is possible during the visit. Further data analysis tools are available.

Sample requirements (Input of users)

https://www.structuralbiology.eu/platform-type/solution-nmr/

https://www.structuralbiology.eu/platform-type/solid-state-nmr/

Services do NOT include

Post collection structure refinement; resonance assignment.

Timelines

On demand.

Capacity

Multiple projects at once are possible.

Provider

Instruct, CERM/CIRMMP, Italy. Instruct-ERIC is a distributed research infrastructure in structural biology, making high-end technologies and methods available to researchers. Instruct-ERIC provides the technical frameworks with which we can interpret molecular and cellular functions. The main experimental technologies that Instruct-ERIC offers are complementary, and increasingly link detailed atomic structure of single molecules or macromolecular complexes with their cellular context. Instruct-ERIC 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.

Lead scientist

Lucia Banci.

Contact

Francesca Morelli, fmorelli@cerm.unifi.it

Description of service

Access to eBIC and OPIC electron microscopy facilities. Capabilities in the cryo-EM Centre eBIC span single particle analysis and molecular and cellular tomography using FEI technology and direct electron detectors. Automation is available for handling multiple samples. In addition, preliminary screening can be done on the Polara instrument, available at the sister OPIC facility. Guidance is available on sample preparation ahead of the use of high-end microscopes and preliminary image collection.

Possible output

A number of imaging detectors are available and their use dependent on the sample - advice is available. Acquisition software is instrument dependent: Krios EPU 1.4.4, Tomo 4.2.1, GMS 2.33; Talos EPU 1.6.0.1340REL, TOMO 4.2.0.4802; Polara Digital Micrograph 1.85, GMS 2.3, SerialEM 3.4. Automated data processing is available onsite and further analytic advice is available via CCP-EM located in an adjacent building.

Sample requirements (Input of users)

Information to follow shortly.

Services do NOT include

Further image analysis.

Timelines

On demand.

Unit of access

2 day shift.

Capacity

On demand. Multiple samples possible.

Provider

Instruct, UOXF/DIAMOND, UK. Instruct-ERIC is a distributed research infrastructure in structural biology, making high-end technologies and methods available to researchers. Instruct-ERIC provides the technical frameworks with which we can interpret molecular and cellular functions. The main experimental technologies that Instruct-ERIC offers are complementary, and increasingly link detailed atomic structure of single molecules or macromolecular complexes with their cellular context. Instruct-ERIC 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.

Lead scientist

Peijun Zhang.

Contact

Dan Clare, daniel.clare@diamond.ac.uk, + 44 1235777501.

Platform Immunocorrelates and System Biology

Description of service

Services include advice on sample selection and experimental design, RNA extraction with a QIA Symphony robot and quality assessment 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. Users can request service(s) that would be of interest to them; the Facility has a particular strength in bioinformatics.

Possible output

Type of analysis to be discussed. For a typical RNA-Seq project: mapping to the transcriptome including QA, expression quantification, differential expression analysis, gene ontology and (un-)supervised classification. Any final and intermediate data generated during the analysis can be provided including comprehensive, publication ready figures and a protocol of the analytical steps. If time permits, possibly integration to other assays or usage of external data from public repositories as validation cohorts is possible.

Sample requirements (Input of users)

If RNA-Extraction with our QIA Symphony robot is requested, input material depends on the RNA/miRNA extraction kit used.

For data analysis, ideally raw data such as compressed fastq files for RNA-Seq should be provided. It is important to provide us with any available per sample quality metrics such as RIN numbers and any batch labels such as extraction dates to improve data analysis.

Services do NOT include

Long term storage of raw data.

Timelines

For RNA extraction the processing time for 200 samples including training is about 2 weeks. Bioinformatics analysis strongly depends on analytical goals and quality of the data, but also on number of samples and number of current projects. A typical 200 sample RNA-seq project requires about 1 week for pre-processing and quantification and 2 to 8 weeks for the actual analysis.

Unit of access

Depends on needs of user: typically RNAseq and/or bioinformatic analysis of data from 1 clinical sample.

Capacity

Only one project can be processed at a given time. Sample size for sequencing based data analysis should be below 1200 samples per project due to storage size limitations.

Provider

University of Oxford (UOXF), Jenner Institute's Transcriptomics Core Facility, UK. 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.

Lead scientist

Professor Helen McShane.

Contact

Dr Julius Muller, julius.muller@ndm.ox.ac.uk, +44 750 8280522.

Description of service

CyTOF Analysis

Related services

ICS analysis, mass cytometry analysis, in vivo imaging, methodology and statistical consultancy, flow and mass cytometry courses, in vivo imaging courses.

Publications related to service

www.ncbi.nlm.nih.gov/pubmed/25704858

www.ncbi.nlm.nih.gov/pubmed/28444973

Possible output

FCS files, single sample analysis and simple global overview of the results.

Sample requirements (Input of users)

Whole blood, frozen PBMCs or frozen isolated cells from different tissues.

Services do NOT include

Establishing and validating new panels of markers in different species. Unsupervised analysis is not provided, but an analysis room with the main software is available at the core facility.

Timelines

The time required for the acquisition is calculated according to the speed of acquisition = 500 cells/second.

Unit of access

One day CyTOF acquisition.

Capacity

58 units of access.

Provider

CEA-IDMIT, France.

Lead scientist

Antonio Cosma.

Contact

Antonio Cosma, antonio.cosma@cea.fr, +33(1)46548757.

Description of service

Modality of access under this proposal: Users can provide human or animal serum, plasma or tissue samples, or cell pellets or supernatants from cell models. These must be extracted prior to analysis either by LU or by the user after appropriate training, including techniques to stop metabolic activity during sampling. The user will choose the metabolomics platforms and experimental design with advice from LU. Users are also advised to reach out to the BMFL.

Related services

Metabolomics can be a valuable tool to combine with animal model studies provided by TRANSVAC2. Complimentary services in Immunecorrelates and systems biology (TNA7).

Publications related to service

  1. Amine method
    Noga, M.J., et al. Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis. Metabolomics 2012; 8: 253-263. (doi:10.1007/s11306-011-0306-3)
  2. Lipid method
    Chunxiu Hu et al., RPLC-Ion-Trap-FTMS Method for Lipid Profiling of Plasma: Method Validation and Application to p53 Mutant Mouse Model. J. Proteome Res., 2008, 7 (11), pp 4982–4991. doi: 10.1021/pr800373m.
  3. Oxylipin method
    Strassburg et al., Quantitative profiling of oxylipins through comprehensive LC-MS/MS analysis: application in cardiac surgery. ANALYTICAL AND BIOANALYTICAL CHEMISTRY 2012; 5:1413-1426. doi: 10.1007/s00216-012-6226-x.
  4. GC (optimized version based on a method developed)
    Koek MM, van der Kloet FM, Kleemann R, Kooistra T, Verheij ER, Hankemeier T. Semi-automated non-target processing in GC × GC–MS metabolomics analysis: applicability for biomedical studies. Metabolomics. 2011;7(1):1-14. (doi:10.1007/s11306-010-0219-6).
  5. QC correction method
    Van der Kloet, F.M. et al., Analytical error reduction using single point calibration for accurate and precise metabolomic phenotyping. , J. Proteome Res., 2009, 8 (11), pp 5132–5141. doi: 10.1021/pr900499r.

Possible output

A dataset (Excel based) containing relative metabolites levels across all samples. In some cases, accurate quantification is possible, where in-house standards are available.

Sample requirements (Input of users)

In agreement with service provider (Users are encouraged to engage with the service provider in experimental design and choosing the correct biology to target). Sample requirements are dependent on the chosen metabolomics platforms. General guidelines include:

In Vitro

  1. Good study design including biological replicates
  2. On average cell pellets containing 100 000 to 1 000 000 cells. (Depended on the cell type used)
  3. Cell quenching procedures must be discussed with the service provider prior to sample collection
  4. Collected samples must be stored at -80°C

In Vivo (Animal models, Human)

  1. Sample handling and collection must be described. All samples must be collected on the same protocol and at the same institution and stored at -80°C.
  2. Metadata to include: Gender, BMI, Known medication (drug usage), Fasting status of sample, Known medical conditions. (Examples include: metabolic syndrome and diabetes)
  3. Different metabolomics platforms require different sample volume.

Services do NOT include

Data analysis.

Timelines

6 months from sample delivery.

Unit of access

One Day, (approx.. 20 samples).

Capacity

70 units of access. Max. 4 projects at the same time.

Provider

Leiden University. 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 (liquid chromatography - mass spectrometry based) 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.

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. https://www.universiteitleiden.nl/en/research/research-facilities/science/biomedical-metabolomics-facility-leiden.

Current BMFL platforms include:

  1. Lipidomic platforms (Targated & Untargated)
  2. Bile acids
  3. Oxylipins / Eicosanoids
  4. Biogenic amines
  5. Acylcarnitines
  6. Central carbon metabolism
  7. Oxidative and nitrosative stress
  8. Endocannibinoids

Lead scientist

Nelus Schoeman and Thomas Hankemeier.

Contact

Nelus Schoeman, j.c.schoeman@lacdr.leidenuniv.nl

Thomas Hankemeier, hankemeier@lacdr.leidenuniv.nl

Tel: 0031 71 527 5682.

Description of service

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.

Related services

NHP dcRT-MLPA to be developed by BPRC.

Publications related to service

Haks MC, Goeman JJ, Magis-Escurra C, Ottenhoff TH. Vaccine. 2015 Sep 29;33(40):5282-8. doi: 10.1016/j.vaccine.2015.04.054. Epub 2015 Apr 24. PMID: 25917681.

Possible output

List or gene expression levels in sample.

Sample requirements (Input of users)

In mutual agreement with service provider: either purified RNA, or sample from which RNA still needs to be extracted.

Services do NOT include

Data analysis.

Timelines

6 months from sample delivery.

Unit of access

Sample to be profiled for expression of 1, 2, 3 or 4 sets of around 50 genes.

Capacity

6 units of access. Max. 2 projects at the same time.

Provider

Leiden Univ. Medical Center (LUMC), Department of Infectious Diseases, The Netherlands. LUMC offers an extended multiplex transcriptome profiling assay (dcRT-MLPA) for monitoring innate, adaptive and inflammatory immune-response signalling gene signatures, which can be used to evaluate and improve immunisation strategies.

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 FP7 projects.

Lead scientist

Marielle Haks and Tom Ottenhoff.

Contact

Marielle Haks, m.c.haks@lumc.nl

Tom Ottenhoff, t.h.m.ottenhoff@lumc.nl

Tel: +31-71-5262620.

Currently not available. Information to follow shortly (available from December 2018).

Description of service

UNISI will perform bioinformatic analysis of RNA sequencing experiments. The set of possible analyses include: 1) comparison of cell populations for the identification of differentially expressed genes; 2) dimensionality reduction for the identification of relevant coordinates; and 3) clustering of subpopulations on the base of gene expression profiles.

Related services

The service is linked with the RNA sequencing service offered by UNISI-LABMM.

Possible output

Data will be provided using standard file formats (bam, csv, vcf).

Sample requirements (Input of users)

Results of RNA sequencing experiments in fastq format, and metadata about the experimental protocol.

Services do NOT include

Designing of the experiments, and quality check of experimental results.

Timelines

The expected pace is 10 RNA samples per week.

Unit of access

Single set of experimental data. The number of necessary samples depend on the analyses required. There is no preliminary restriction on the minimum/maximum number of samples analysed.

Capacity

About 5 units of access will be provided. Multiple projects can be accepted at once. The expected turnover is 1 unit of access every 1-2 weeks, depending on the complexity of the requested analyses.

Provider

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, molecular microbiology, genetic engineering and NGS sequencing.

Lead scientist

Antonio Vicino.

Contact

Simone Furini, simone.furini@unisi.it, 0039-0577-585297.

Description of service

UNISI will provide 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 Cytometric bead assay. Both technologies allow the simultaneous detection of multiple factors in serum, plasma and tissue culture supernatants. UNISI will receive murine or human samples from users. Multiple biomarkers, such as cytokines, chemokines and growth factors will be detected using one of the available multiplex system to test up to 46 murine and 53 human analysts. Users will decide how many proteins will be tested and the analysis will be carried out by our technicians. Data analysis can be also performed.

Publications related to service

  1. Ciabattini A, et al. Modulation of Primary Immune Response by Different Vaccine Adjuvants. Front Immunol. 2016 Oct 17;7:427. eCollection 2016.
  2. Fiorino F et al. Prime-boost strategies in mucosal immunization affect local IgA production and the type of th response. Front Immunol. 2013 May 29;4:128. doi: 10.3389/fimmu.2013.00128. eCollection 2013.

Possible output

Raw data in electronic format (i.e .xlsx o .xls); graphs of results if requested.

Sample requirements (Input of users)

Serum, plasma and tissue culture supernatants (10 ul for sera and plasma samples, 50 ul for culture supernatant).

Services do NOT include

Costs for shipment of samples.

Timelines

3 days from the receiving of the samples to perform the assay; - 2 days of data analysis (if requested by the users); (if the user requests particular panels, 15-30 days should be considered for the shipment of reagents).

Unit of access

Multiplex cytokine analysis including 5 soluble factors; (different number of soluble factors can be requested directly to the provider).

Capacity

7 units of access.

Provider

University of Siena - Department of Medical Biotechnology, Laboratory of Microbial Immunity, Italy. 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 Microbial Immunity is part of this Department, and its research focuses on host-pathogen interaction, recombinant vaccines and vaccine immunology.

Lead scientist

Donata Medaglini.

Contact

Annalisa Ciabattini, annalisa.ciabattini@unisi.it, 0039-(0)577-233100.

Description of service

UNISI will provide a targeted RNA sequencing service. If necessary, RNA will be extracted from PaxGene tubes. RNA will be quantified by fluorimetry, retrotranscribed and then sequenced using Ion AmpliSeq™ Transcriptome Human Gene Expression Kit on the “Ion Proton™” (Thermo Fisher) sequencing platform. The expression level of 20,802 human genes will be quantified. A minimum of 8 million reads/sample will be guaranteed. RNA obtained from any human sample can be sequenced with this protocol.

Publications related to service

The following publication describes the protocol used for sequencing:

Li W, Turner A, Aggarwal P, Matter A, Storvick E, Arnett DK, Broeckel U. Comprehensive evaluation of AmpliSeq transcriptome, a novel targeted whole transcriptome RNA sequencing methodology for global gene expression analysis. BMC Genomics. 2015 Dec 16;16:1069. doi: 10.1186/s12864-015-2270-1. PubMed PMID: 26673413.

Possible output

Data will be provided in form of counts table (csv file) and/or bam files.

Sample requirements (Input of users)

Frozen total RNA from any human sample and/or human derived cell-cultures. Minimum input RNA: 200 ng, minimum RNA concentration 10 ng/ul (quantified by a fluorimetric method, e.g. Qubit). RNA should preferably be suspended in water or 5mM Tris (pH 7.5-8.5) and shipped on dry ice in properly labelled DNAse-, RNAse-free 1.5 ml tubes. Users may also provide frozen PaxGene tubes containing blood from patients/volunteers.

Services do NOT include

Costs for shipment of samples, additional Bioinformatic analyses.

Timelines

The expected turnaround time will be 2 weeks for every 16 RNA samples plus an additional week for every other 16 samples. Consider one additional week if providing PaxGene tubes.

Unit of access

8 RNA samples to be sequenced (the users should preferentially provide samples in multiples of 8).

Capacity

20 units of access. Samples from multiple user will be accepted, but processing will be delayed.

Provider

University of Siena - Department of Medical Biotechnology, Laboratory of Molecular Microbiology and Biotechnology, Italy. The Department of Medical Biotechnologies 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, molecular microbiology, genetic engineering and NGS sequencing.

Lead scientist

Donata Medaglini.

Contact

Francesco Santoro, santorof@unisi.it, 0039-(0)577-233101.

Description of service

Mass Spectrometry Imaging (MSI). The Metabolomics & Proteomics Technology Unit will offer localizomics approaches based on MS Imaging on tissue/organs slices (or on in-vitro cell cultures), either in targeted MS (i.e. drug and metabolites distribution) or in untargeted high resolution (HR) MS (metabolite profiling).

Applied training in Mass Spectrometry Imaging, based on the DESI technology, is also proposed. The samples will be analysed on the MS Imaging platform by our qualified personal.

Related services

MS imaging service is complementary to Metabolomics, Proteomics and PK/PD services offered by TRANSVAC2.

Possible output

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.

Sample requirements (Input of users)

Users can provide frozen slices of tissue, entire frozen tissue sample ready to be sliced, or cultures of cells.

Detailed sample requirements will be discussed with the users before the access.

Timelines

Timelines and service duration will be discussed with users and established on a case-by-case basis.

Unit of access

The unit of access is 1 MSI experiment, (based on targeted analysis, for a 1cm square surface, with a minimum of 10 slices by access).

For training, the unit of access is a two-day course.

Capacity

No limitation in the quantity of access, as service is on a pay-for-service basis. Access, number of samples and service duration will be established on a case-by-case basis. The MSI platform has the capacity to carry on multiple projects.

Provider

BIOASTER, Metabolomics & Proteomics Technology Unit, France. BIOASTER is a non-for-profit Technological Research Institute dedicated to applied Microbiology and Infectious Diseases. Its missions are to lead innovative collaborative projects, with and for public and private partners and to conceive and develop innovative and high value technology solutions.

The Metabolomics & Proteomics Technology Unit activity focus 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.

Lead scientist

Kristin Hennig.

Contact

Frédéric Bequet, frederic.bequet@bioaster.org, +33 481113740.

Platform Animal Models

Description of service

Immunogenicity study (1 NHP)

Related services

ICS analysis, mass cytometry analysis, in vivo imaging, methodology and statistical consultancy, flow and mass cytometry courses, in vivo imaging courses.

Publications related to service

www.ncbi.nlm.nih.gov/pubmed/28760882

www.ncbi.nlm.nih.gov/pubmed/28352649

www.ncbi.nlm.nih.gov/pubmed/28203239

www.ncbi.nlm.nih.gov/pubmed/27009957

www.ncbi.nlm.nih.gov/pubmed/26678013

www.ncbi.nlm.nih.gov/pubmed/25839103

Possible output

Project management, raw data for clinical follow-up, tolerability assessment, CBC, blood chemistry, antibody binding and ELISPOT, cryopreserved plasma, serum, mucosal fluids and cells.

Sample requirements (Input of users)

Immunogen and adjuvant - if any - with specification datasheets.

Services do NOT include

Enhanced analysis (ICS, luminex, neutralisation assays), challenge studies.

Timelines

Depending on the immunisation schedule, maximum 6 months.

Unit of access

1 NHP.

Capacity

18 units of access. Possible to carry multiple projects at once with a maximum of 18 NHP.

Provider

CEA, IDMIT, France.

Lead scientist

Raphael Ho Tsong Fang.

Contact

Raphael Ho Tsong Fang, raphael.ho-tsong-fang@cea.fr, +33(1)46548757.

Description of service

Access to FlowCy Tech: 1. ICS (Intracellular Cytokine Staining) 2.CyTOF Analysis.

Related services

ICS analysis, mass cytometry analysis, in vivo imaging, methodology and statistical consultancy, flow and mass cytometry courses, in vivo imaging courses.

Publications related to service

www.ncbi.nlm.nih.gov/pubmed/23184609

www.ncbi.nlm.nih.gov/pubmed/25704858

www.ncbi.nlm.nih.gov/pubmed/28444973

Possible output

FCS files, single sample analysis and simple global overview of the results.

Sample requirements (Input of users)

  1. Cells (frozen or fresh PBMC) and antigens to be tested with specification datasheets.
  2. Whole blood, frozen PBMCs or frozen isolated cells from different tissues.

Services do NOT include

  1. Integration of the analysis with other datasets
  2. Establishing and validating new panels of markers in different species. Unsupervised analysis is not provided, but an analysis room with the main software is available at the core facility.

Timelines

  1. Two weeks provided all the reagents are available (cells, antigens and antibodies)
  2. The time required for the acquisition is calculated according to the speed of acquisition = 500 cell/second

Unit of access

  1. 1 staining
  2. 1 day CyTOF acquisition

Capacity

  1. 300 units of access
  2. 58 units of access

Provider

CEA, IDMIT, France.

Lead scientist

Antonio Cosma.

Contact

Antonio Cosma, antonio.cosma@cea.fr, +33(1)46548284.

Description of service

SSI offers vaccination studies in mice including 1-2 control groups and full immunogenicity analysis including CMI and humoral immunogenicity using Flow cytometry (B and T cells) and ELISA (cytokines and antibodies).

Possible output

Full immunogenicity evaluation of test vaccines.

Sample requirements (Input of users)

Vaccines including controls and if needed test antigens for re-stimulation studies.

Services do NOT include

Optimization of vaccine formulations before injection.

Timelines

4 months including analysis and report.

Unit of access

Immunogenicity testing including 6 mice/grp (1 unit) compared to pos. and neg. controls.

Capacity

7 projects. 2-3 projects per year.

Provider

The Department for Infectious Disease Immunology at SSI is a leading partner in European and North American vaccine collaborations e.g. EDCTP, EU Framework programs, AERAS and the Gates Foundation. The department has approximately 40 staff, including immunologists, molecular biologists and protein chemists with access to state-of-the-art animal facilities. The core expertise of the department is identification of vaccine antigens, and analysis of vaccine-induced immune responses, in particular within the field of TB. In addition, the department has extensive experience with adjuvant research and development including approximately 50 papers relating to adjuvant mechanisms. The department has an active clinical research program including the analysis of immune responses to vaccination or different infectious diseases e.g. M. tuberculosis in humans and animals.

Lead scientist

Dennis Christensen.

Contact

Dennis Christensen, den@ssi.dk, +45 32683804

Description of service

As partner of TRANSVAC2, WBVR will provide access to their animal facilities (Lelystad) to carry out immunogenicity and efficacy studies of new candidate vaccines and/or of novel vaccination (administration) strategies in pigs, cattle, ferrets or other animal species. Efficacy studies depend on the availability of the challenge model and can be performed in biosafety containment up to BSL3. The access will comprise purchase of animals, the housing and animal care and biotechnical expertise for administration and sampling. Scientific support will include advice on experimental design and methodology, documentation of results for all experiments conducted during the project, and appropriate sampling and conservation of samples. Laboratory analyses are included to primary read-outs like haematology, immunology, pathology, but need to be defined on a case by case evaluation. WBVR will also provide the required legal approvals and ethical approval.

Possible output

Study plan, animal experiment approval by the institutional AWB and the Dutch Central Authority for Scientific Procedures on Animals (CCD), raw data as excel file and a summarizing report on the study, biological samples.

Sample requirements (Input of users)

Well described vaccine formulations and/or SOP for vaccine formulation; user is responsible for transport of vaccines.

Services do NOT include

Extended immunology or molecular assays or bioinformatic analyses are not included, but can be offered.

Timelines

Depending on the type of animal study; if approval by the Dutch Central Authority for Scientific Procedures on Animals (CCD) is necessary at least 4 months until start of the study and 2 months after end of the in-life phase for analysis and reporting.

Unit of access

1 study.

Capacity

3 units of access. Capacity to work on several projects depends on the requested service.

Provider

Wageningen Bioveterinary Research (WBVR) is part of Wageningen University&Research (WUR/SWR), Lelystad, The Netherlands, a Dutch organisation combining academic institutes and research institutes in the field of life sciences.

Lead scientist

Dr. Norbert Stockhofe-Zurwieden, DVM, Spec. Vet. Pathol.

Contact

Dr. Norbert Stockhofe-Zurwieden, Norbert.Stockhofe@wur.nl, 0031 (0)320238238.

Description of service

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 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 and formulation. Within the framework of TRANSVAC2, the HZI will offer access in the form of pre-clinical studies in the murine system to assess the immunogenicity, safety and efficacy of specific vaccine formulations. The access includes animal breeding, housing, caretaking and biotechnical expertise for mouse studies on a vaccine candidate (provided by the user) including sampling and standard immune monitoring to carry out validation experiments of the new vaccine candidate or vaccination strategies of the potential user. The HZI will also provide access to laboratory and animal facilities up to BSL3 (including the gnotobiotic unit) and conventional, modified (e.g. knockout, knock-in, reporter) and humanised (e.g. immune system) mice as animal models. More specifically, the access will comprise: (i) the purchase and/or breeding of animals, including housing and animal care; (ii) support in the area of vaccinology to advice on the experimental design, vaccination protocol and methodology for the immune monitoring; (iii) conduction of immunizations and subsequent monitoring for the appearance of acute side effects; (iv) the sampling of blood and/or organs for the characterization of the immunogenicity of the corresponding formulation; (v) performance of standard tests to characterize antigen-specific humoral and cellular immune responses at both systemic and mucosal territories (e.g., total antibodies and IgG subclasses in sera, secretory IgA, Th responses, CTL, Elispots, cytokines, etc.); (vi) documentation of results for all experiments conducted during the project; (vii) access to raw data; (viii) appropriate conservation and storing of biological samples, if required; (ix) data analysis in collaboration with external users; and (x) advice and support for legal and ethical requirements, including preparation of applications for animal studies. Each unit of access will correspond to 5-10 animals per immunization group. The number of the animals per group might slightly change depending on the broadness/complexity of the immune monitoring and/or experimental setting.

Related services

TNA 2 (Adjuvants and delivery systems service - mucosal adjuvant platform)

Possible output

A summary of the results obtained with each formulation will be provided.

Sample requirements (Input of users)

Material (i.e. vaccine) suitable for preclinical in vivo immunisation studies and vaccine antigen for the assays will be provided by the user.

Services do NOT include

Vaccine/antigen production.

Timelines

Approximately 10-12 weeks (experiment duration). This might be affected by the experimental conditions (e.g. evaluation of memory responses).

Unit of access

1x Characterization

Capacity

6 units. A max. of 2 projects at once.

Provider

Helmholtz Centre for Infection Research (HZI), Germany. 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 the 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. In order 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). The HZI carries out research into infectious diseases, investigating the mechanisms of pathogenesis to develop new strategies for prevention, diagnosis and therapy. The team at the HZI providing access through the project has access to state-of-the-art laboratories and animal facilities with BSL2 containment, flow cytometry and cell sorting facilities, histopathology and in vivo imaging (IVIS). The HZI animal facilities accommodate ~20.000 mice and provide containment up to BSL3.

Lead scientist

Carlos A. Guzman, MD PhD.

Contact

Carlos A. Guzman, MD PhD, carlos.guzman@helmholtz-hzi.de, +49 531 6181 4600.

Description of service

BPRC will provide will provide access to adult, MHC-typed macaques for immunogenicity/adjuvanticity evaluation for typical studies of up to 26 weeks and up to containment level BSL3. The service includes baseline assessments and post-vaccination follow-up by biosample collection (up to 12 time points in total) and banking for at least up to 2 years after the study, as well as standard humoral and/or cellular immunology tests. Users may suggest specific assays for selected time points. These may include but are not limited to vaccine specific and advanced multi-label flow cytometric analyses. A typical immunisation protocol might contain up to three (prime-boost) immunisation events. The access and services include applications for regulatory and/or ethical approval (by European and Dutch law), optimisation of study design and the summary of results in a study report. Additional study objectives, such as challenge or advanced immunological assessments (imaging, flow cytometry, etc.) and the addition of more animal units, may be negotiated and offered under institutional access rules.

Related services

Protein and adjuvant analysis and production services offered under TNA 1, 2, 3 and 6 may be explored. TNA7 provides analytics services that may be suitable analysis of biosamples obtained from the study.

Possible output

Study Report and relevant raw Data. Biological samples can be made available for further analyses outside the infrastructure and/or in TNA3 and/or by user.

Sample requirements (Input of users)

The user will be responsible for the timely delivery of GMP grade test substances (and reagents (e.g. specific antigens) when it applies).

Services do NOT include

Costs for shipment of samples will be the responsibility of the User.

Timelines

Duration of one vaccine safety and immunogenicity profiling experiment is maximally 26 weeks. Including preparatory work, reporting and possible challenge, one study may take up to one year to be completed.

Unit of access

Vaccine safety and immunogenicity profiling per animal.

Capacity

15 animals. Typically, evaluation of one vaccine will require one group of minimally 5 animals. Multiple vaccines can be evaluated in parallel.

Provider

Foundation Biomedical Primate Research Centre (BPRC), the Netherlands. Biomedical Primate Research Centre (BPRC) is the largest European biomedical primate research facility and has a long and successful collaborative track record with institutions in Europe and elsewhere. BPRC applies molecular, biochemical and immunological know-how to provide new vaccine and therapeutic strategies for malaria, tuberculosis, HIV, hepatitis C and other infectious diseases. BPRC has considerable experience in preclinical vaccine development, has played a leading role in taking malaria vaccines to the clinic, and in establishing comparative assay systems for malaria and other vaccines.

BPRC houses a large colony of rhesus macaques and marmosets housed in state of the art facilities, has extensive knowledge on primate disease models, immunology, physiology and experience with the specific requirements for housing and handling of primates. All requirements for high level immunological determinations (including ELISPOT reader, FACSAria, LSRII system fully equipped, Luminex, multi-label plate reader) are on site and in routine use.

Lead scientist

Frank Verreck.

Contact

Frank Verreck, verreck@bprc.nl, +31 15 284 2657.

Description of service

PHE will provide access to the ferret model of influenza at BSL2 as part of TNA8 Animal models platform.

Related services

Users may wish to use analytics services to assess purity of vaccine candidates (TNA3).

Publications related to service

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094090

Possible output

Report detailing clinical parameters of disease, virology (nasal wash virus titres), serology, IFN-gamma ELISA, IFN-gamma Elispot.

Sample requirements (Input of users)

User to provide vaccine samples of suitable purity and quality for vaccination of ferrets. Documentation should be provided confirming quality control (freedom from pyrogens, freedom from bacterial contamination). User to provide antigen for immunological assays if required.

Services do NOT include

Optional: additional groups of ferrets for lung/tissues; virus neutralisation titres; histopathology; immunogenicity studies.

Timelines

Maximum study duration 12 weeks. Advance notice of 3-4 months required before start of study.

Unit of access

The unit of access comprises a vaccination/challenge study with 3 groups of 6 ferrets (control and 2 vaccine groups), to include intra-nasal challenge with influenza virus, monitoring of virus load (nasal washes), disease progression and immune responses (antibody, IFN gamma ELISA and ELISpot).

Capacity

1 unit of access.

Provider

Public Health England (PHE), Porton, England. 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.

Lead scientist

Anthony Marriott.

Contact

Anthony Marriott, anthony.marriott@phe.gov.uk, (+44)1980 612371.

Description of service

  1. PFIE will provide access to its facilities for immunogenicity and efficacy studies in pigs or sheep (as well as other species if needed), according to users’ requirements. Experiments can be carried out in open barns or in BSL2 or BSL3 suites for laboratory and large animals as well as in isolators, for small species.
  2. VIM offers the following services for pig/ruminant samples: ELISA, FACS, in vitro restimulation cultures, qRT-PCR analysis, fluorescence laser microscopy, 3-4 laser cytometry (405, 488, 560 and 640 nm) allowing the simultaneous monitoring of up to 20 parameters. We produce and analyse live and inactivated viruses in our BSL2 and BSL3 facilities. Immunogenicity and efficacy studies in pig (influenza) and sheep (RSV) with a focus on skin vaccination and extended monitoring of humoral and cellular immune responses in the blood and lung.

Publications related to service

    • Herry V, Sci Rep. 2017 Jun 13;7(1):3441.
    • Bernelin-Cottet C, Front Immunol. 2016 Dec 26;7:641.
    • Martinelle, L., Veterinary research, 2016, 47 (1): 73.
    • Riou M., International Journal of Antimicrobial Agents, 2016, 47 : 77-83.
    • Beck C, Biomed Res Int. 2015;2015:678084.
    • Guillon A, PLoS One. 2015 Nov 23;10(11):e0143459.
    • Laloy E, BMC Vet Res. 2015 Aug 22;11:221.
    • Sarradin P, PLoS Pathog. 2015 Aug 6;11(8):e1005077.
    • Deloizy C, Sci Rep. 2017 Aug 9;7(1):7639.
    • Bernelin-Cottet C, Front Immunol. 2016 Dec 26;7:641.
    • Deloizy C, Dev Comp Immunol. 2016 Dec;65:31-40.
    • Maisonnasse P, Mucosal Immunol. 2016 Jul;9(4):835-49.
    • Vu Manh TP, Front Immunol. 2015 Jun 19;6:299.
    • Marquet F, J Immunol. 2014 Dec 15;193(12):5883-93.
    • Pages N, PLoS One. 2014 Jan 8;9(1):e83683.
    • Ruscanu S, J Virol. 2013 Aug;87(16):9333-43.

Possible output

  1. All data recorded during animal experiment will be supplied in a final report, i.e. clinical observations and monitored parameters like body temperature, weight, haematology or biochemistry analysis, animals' behaviour or any other information required by users.
  2. Raw or partly analysed ELISA, Elispot, Facs , qRTPCR, Microscopy data.

Sample requirements (Input of users)

  1. Users should provide inocula and/or vaccines they want to test during animal experiments. Final steps of their preparation can be performed in the facility's lab if necessary (extemporaneous dilution for example).
  2. Serum, frozen PBMC or solenocytes, dissociated frozen tissue cells.

Services do NOT include

Access does not include shipping of biological (inocula, samples at the end etc.) or technical material.

Haematological and biochemical analyses are not included as well.

Timelines

Duration of an access to the platform can range, for instance from 2 weeks to 3 months, according to the user's needs. Ideally, experiments should end about 3 months before the end of the Transvac2 project.

Unit of access

  1. The unit of access is defined as one day.
  2. One unit of access will correspond to one week of laboratory experiment.

Capacity

  1. A total of 160 days of access. Thanks to the number of experimental rooms available, PFIE can carry out several projects at the same time, provided they have been scheduled in advance.
  2. VIM will provide twelve units of access during the project. Max. 4 can be run in parallel.

Provider

INRA VIM/PFIE, France.

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.

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 and influenza.

Lead scientist

  1. Pierre Sarradin.
  2. Nicolas Bertho.

Contact

  1. Pierre Sarradin, pierre.sarradin@inra.fr, +33 674 654 234.
  2. Nicolas Bertho, nicolas.bertho@inra.fr, +33 134 652 611.

Description of service

As partner of TRANSVAC, IRTA will provide access to their animal facilities (CReSA) to carry out safety and immunogenicity studies of new candidate vaccines and/or of novel vaccination (administration) strategies in pigs, ferrets and other large animal species. The access will comprise purchase of animals, the housing and animal care and biotechnical expertise for administration and sampling. Scientific support will include advice on experimental design and methodology, documentation of results for all experiments conducted during the project, and appropriate sampling and conservation of samples. In depth laboratory analyses can be included or not, offering at this way three types of access: only animal facilities, only laboratory facilities, and both. IRTA will also provide the required legal approvals and ethical approval.

Publications related to service

List of publications at IRTA (CReSA): www.ncbi.nlm.nih.gov/pubmed/?term=cresa

Possible output

The deliverable for these studies will be raw research data. In case the user may have contact with or own BSL3 laboratories, samples can be sent to them in the conditions fitting international requirements.

Sample requirements (Input of users)

The user will be responsible for the timely delivery of test substances, as well as for the reagents to perform the immune monitoring (e.g. antigens, peptides). Depending on the immunization route and animal species used, different volume restrictions might apply.

Services do NOT include

Extra-studies not included in the general framework of the access units. If needed to be performed in situ, a particular quotation will be prepared by IRTA and they will be executed if previously accepted by the user. Shipment of samples are not included.

Timelines

12 weeks; the planning of the study, in touch with the provider, should be at least 12 weeks before start as well.

Unit of access

Three modalities are considered: ANIMAL FACILITIES (one access unit is equivalent to 2 animal experimental boxes during 1 month), LABORATORY (one access unit is equivalent of 1 laboratory area of NBS2 or NBS3 during 1 month) and ON DEMAND (one access unit is the combination of the two previous access units).

Capacity

Animal facilities modality: 3; Laboratory modality: 3; On demand modality: 2. There is the possibility to carry multiple projects at once, depending on the general availability of the facilities.

Provider

Institut de Recerca i Tecnologia Agroalimentàries (IRTA), CReSA, Spain. IRTA is a public company of the Government of Catalonia in Spain. The IRTA research program on animal health is conducted by the Centre de Recerca en Sanitat Animal (CReSA), which operates under a quality assurance system with ISO 17025 and GLP. CReSA building of IRTA has 1200 m2 of BSL3+ facilities that can accommodate large animals including camels, an insectarium, 300 m2 of fully equipped BSL3 facilities with a cell sorter and 710 m2 of BSL2 laboratories. The mission of IRTA-CReSA is to contribute to the advancement of scientific and technical knowledge on animal health by research, knowledge transfer and services to public and private bodies. The long-term objective is to globally improve all aspects of animal health that influence the agrifood sector and public health. IRTA has participated in many Spanish and European research projects, focusing on different aspects on animal health and their implications on public health.

Lead scientist

Joaquim Segalés.

Contact

Xavier Abad, xavier.abad@irta.cat, 0034934674040 Ext. 1764

Platform Clinical Trial Support

Description of service

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.

Related services

Regulatory support for vaccine development.

Possible output

Submission and follow-up with the regulatory authorities and ethics committees.

Sample requirements (Input of users)

The user will have to provide the Clinical trial application dossier as submitted in the sponsor country to be adapted and submitted in the other participating countries.

Services do NOT include

The submission in sponsor countries and clinical trial management services are not included in this TNA.

Timelines

Timelines according to regulation.

Unit of access

Days of support with expertise.

Capacity

245 days. Several projects can be performed at the same time.

Provider

ECRIN partners in the involved countries and Ecrin Core team in Paris. 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’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.).

Lead scientist

Christine Kubiak.

Contact

Christine Kubiak, christine.kubiak@ecrin.org, + 33180058628.

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