BIOVACSAFE – Newsletter December 2016 Issue number 8 BIOVACSAFE has been extended to 2018We are very pleased to inform you that the European Commission has approved the 12 months no cost extension of the BioVacSafe project until February 2018. All partners of the BioVacSafe project will thus have the opportunity to obtain more exciting results in the coming year. Subscribe to this newsletter BIOVACSAFE is developing anInnovative DatabaseThe BioVacSafe DATABASE (BioVacSafe DB) is a system based on innovative IT infrastructure to safely capture, store, access, regulate and analyze BioVacSafe data. The BioVacSafe DB consists of IT solutions developed to allow BioVacSafe participants to generate clinical, pre-clinical and biomarker data and perform integrated systems biology analysis.
The BioVacSafe DB will enable the harmonization of data capturing across the project partners, and it is an important starting point for the further development of a common DB with EFPIA partners having access to the new databases as read/consult. On 9th December, a Demonstration Webinar was held to show the latest user interface and capabilities of the BioVacSafe DB. Read more about BIOVACSAFE DATABASE…. The BioVacSafe DATABASE is part of the BioVacSafe Data Management System (DMS). It is being designed and developed at Imperial College Data Science Institute as the first standards compliant general-purpose data management system for translational research data. The key innovation in the creation of this database was to provide a systematic and rigorous implementation of the current standards and regulatory requirements to streamline the process of data integration and harmonization across workpackages. To this goal IMPERIAL has set out to design and develop a new database that was modeled on a newly developed hybrid data model that integrates clinical and biomarker assays (omics) standards for reporting data and meta-data elements. The BioVacSafe DB aims to streamline the process of integration of clinical, pre-clincal and biomarker data to facilitate mining and analysis of relevant immunosafety data for the evaluation of biomarker profiles.
BIOVACSAFE Workshop on
“Integration of Human Omics”
In the BioVacSafe Project, clinical and “omics” data are integrated to analyze the response after vaccination and identify safety biomarkers. The BioVaSafe Integration of Clinical and Omics Data Workshop took place in Berlin on 2nd December in order to discuss the results of the Biovacsafe clinical trials and the integration of transcriptomics and metabolomics data.BIOVACSAFE Partners’ ProfilesIn every biannual newsletter the profile of some of BioVacSafe’s research partners is highlighted. In this edition you will meet the
Chalmers University of Technology in Gothenburg, Sweden, the Statens Serum Institut in Copenhagen, Denmark and the Ghent University inGhent, Belgium
Chalmers University of Technology
Chalmers University of Technology (CHALMERS) is a Swedish University located in Gothenburg. Chalmers is one of the oldest technical University in the Scandinavian countries, found in 1829 by a donation of William Chalmers. The focus of education and research at Chalmers are primarily on the development of technology, natural and maritime sciences, architecture and other management areas. Chalmers has several partnerships from major industrial companies operating in the Gothenburg area i.e., Ericsson, Volvo and SKF as well as many European and U.S. Universities. Within the BioVacSafe project, the Nielsen’s team from the division of Systems and Synthetic Biology (http://www.sysbio.se/) at the Department of Biology and Biological Engineering is responsible for data management system (WP5) and metabolomics (WP7).
Nielsen’s team from the division of Systems and Synthetic Biology at the Department of Biology and Biological Engineering (CHALMERS), working in BioVacSafe
Read more about CHALMERS’s outputs…. CHALMERS is involved in WP5 by designing and implementing a web-based platform that will integrate different types of data, such as transcriptomics, metabolomics and clinical data generated by different partners of BioVacSafe. They have been working closely with Imperial College London to achieve this objective. The BioVacSafe web-based platform was designed using “PIANO” as a main tool for data analysis. The scope of “PIANO” have been extended to analyze (un- or targeted) metabolomics data with a future vision to integrate clinical data. The web-based platform has been tested with dummy datasets and is now waiting for incorporation of real clinical datasets after formalizing the data usability and compliance.Furthermore, within WP7, CHALMERS has completed the analysis of 549 serum samples by untargeted and targeted analysis where the samples were taken from placebo (220 samples), Fluad (209 samples) and Stamaril (120 samples). The sampling points were considered from both In- and Out-patient stay. The preliminary results from the untargeted analysis by UHPLC-qTOF, clearly shown that there is an effect of time after vaccination, and that this effect is vaccine dependent. The response is linked to the circadian rhythm. Matching time points between the vaccinated groups (Fluad or Stamaril) with the placebo group resulted in identification of metabolites that can be used as biomarkers for each specific vaccine. This could indicate that there exist vaccine dependent metabolic responses.
Statens Serum Institut (SSI)
The adjuvant research team from the Department of Infectious DiseaseImmunology of SSI, working in BioVacSafe SSI has up till now designed and optimized eight qPCR biomarker sequences for cytokines/chemokines initially selected as important safety biomarkers during infection and immunization, namely: IL-6, IL-8, TNF-a, IP-10, INF-a, CCL-2, Serum Amyloid A and CCL2. The presence of these biomarkers have been confirmed in a number of vaccination and influenza challenge studies in ferrets and data is available for correlation to other species. The SSI group is currently working on a publication including these results.Read more about Statens Serum Institute…. It is noteworthy that Statens Serum Institut (SSI) strives to be a highly regarded and recognized international research, production and service enterprise. In line with this aim, the Department for Infectious Disease Immunology at SSI is a leading partner in European & North American vaccine collaborations e.g. EDCTP, EU Framework programs, AERAS and the Gates Foundation. The department has a staff of approximately 40, including immunologists, formulation scientists, molecular biologists and protein chemists with access to state of the art animal facilities. The core expertises for the department are identification of vaccine antigens, design of novel vaccine adjuvants including dissection of mechanistic aspects and analysis of vaccine-induced immune responses. In addition, the department has an active clinical research program and expertise within analysis of immune responses to vaccination or different infectious diseases e.g. M. tuberculosis in humans and animals. The department has been inventor of three TB vaccines, one chlamydia vaccine and two adjuvant systems which are all under clinical phase I and II trials or preclinical toxicology evaluation. The adjuvant research group has over the years been involved in several national and EU sponsored collaborative projects where development of novel influenza vaccines or evaluating vaccine safety have been major subjects. These include Center for nano-vaccines, FLUSECURE, UNISEC and BioVacSafe. SSI influenza network in Europe is thus widespread and it has several collaborations with focus on translational influenza research. This includes a number of collaborations using the ferrets for testing vaccine efficacy and safety. The ferret model has for long been the preferred model for testing human influenza vaccines, main reason being that ferretsshare host range, clinical symptoms and pathological changes in the respiratory tract with humans. On the other side, the ferret model is difficult to work with when it comes to monitoring immune responses. The serum antibody responses to influenza infection and vaccination are much similar in humans and ferrets and the methods are well established. However, the ferret model has impressively little tools when it comes to monitoring innate and adaptive cell mediated immune responses. Vaccine safety and efficacy determined in the ferret model therefore has to rely on clinical symptoms and humoral responses.
Ghent University (UGENT), one of the five universities in Flanders (Belgium), is one of the major research universities in Belgium. The Center for Vaccinology (CEVAC) is a research unit within the Department of Clinical Pathology, Microbiology and Immunology (Faculty of Medicine and Health Sciences, UGENT), that contributes to modern vaccine development and evaluation. The Center consists of two separate but intensely interacting and complementary entities, CEVAC Clinical Trial Unit and CEVAC Core Laboratory. CEVAC activities started in 1986 and since then the unit was headed by Geert Leroux-Roels, Professor of Medicine and who acts as co-leaders of Work Package 1 (WP1) and member of the Steering Committee of the BioVacSafe consortium. In the BioVacSafe project, CEVAC is involved in Work Package (WP) 1 by conducting human clinical studies to discover and characterize biomarkers of vaccine safety.Read more about Ghent University’ s outputs…. UGENT’s contribution to BioVacSafe project as part of Work Package 1 involves both CEVAC Clinical Trial Unit and CEVAC Core Laboratory. CEVAC Clinical Trial Unit has conducted two large studies in which 240 healthy volunteers aged between 18 and 45 years have received one dose an adjuvanted influenza vaccine (FLUAD, n=228) or a placebo(12) in one study and one dose of a [tetanus/diphtheria/acellular pertussis] combination vaccine (Boostrix, n=200) and placebo (40) in the second study. Blood samples have been drawn before vaccination and on selected moments
after vaccination to study hematological, biochemical, immunological and gene expression changes following vaccine administration. A final study to be conducted in the CEVAC Clinical unit will be an influenza vaccine study that parallels a controlled infection challenge study that is being conducted at Imperial College London. This final study is designed to specifically complement the readouts from the human challenge infection will be conducted at Ghent University.
CEVAC Clinical team at the Departmentof Clinical Pathology, Microbiology andImmunology (Faculty of Medicine and HealthSciences, UGENT).
Whereas CEVAC Clinical Unit takes care of the clinical trial conduct and sample collection for analyses and biobanking purposes, CEVAC Core Lab determines the vaccine antigen-specific immune responses in the vaccines of all three trials before and on selected time points after vaccination.
CEVAC Core Laboratory team at the Department of Clinical Pathology, Microbiologyand Immunology (Faculty of Medicine and Health Sciences, UGENT).
Humoral and cell-mediated immune (CMI) responses will be measured using standardized and validated techniques. Analyses of the many data on clinical, metabolic, immunological and gene expression responses will hopefully reveal the existence of correlations between the occurrence and severity of local and/or systemic adverse events to a vaccine dose and the pre-vaccination immune status or magnitude of the post vaccination immune response. UGENT is proud to be part of the important and ambitious BioVacSafe Consortium. Nineteen partners are collaborating and committed to develop new tools that will improve the evaluation and monitoring of vaccine safety. By the way, if you are interested in Ghent University’s profile, it was founded in 1817 by King William I of the Netherlands, Prince of Orange. With a total of 36,000 students and 9,000 staff members, UGENT has 11 faculties, which offer a wide academic portfolio, including courses in every scientific discipline, and a research investment which averages around £180million annually. Ghent University ranks 62nd in the 2016 Academic Ranking of World Universities (Shanghai ranking). Within the Department of Clinical Pathology, Microbiology and Immunology, CEVAC boasts participation in more than 200 clinical vaccine evaluations and it has contributed to the development and evaluation of vaccines against hepatitis B, the first combined hepatitis A-B vaccine, a therapeutic vaccine against hepatitis C, vaccines against cervical cancer, herpes simplex, HIV and tuberculosis. As stated above, the Center consists of CEVAC Clinical Trial Unit and CEVAC Core Laboratory, which are located in different buildings but both on the campus of the Ghent University Hospital. This proximity allows for an intense and excellent logistic and scientific interaction between the units and guarantees a perfect treatment and conservation of the precious study samples that are collected. The Clinical Trial Unit, through the nature of its clinical activities administratively linked to the Ghent University Hospital, conducts Phase I and Phase I/II trials of candidate vaccines against a variety of infectious diseases that have been developed by industrial sponsors. The execution of each level of the clinical study is performed according to GCP standards. The team consisting of three MD’s, 5 registered nurses, two administrative assistants is coordinated by Mrs. Fien De Boever. The Immunology Core Laboratory, administratively linked to the UGent, is a GCLP compliant laboratory that provides central lab services to both industrial and academic research partners. These services consist mainly, but not exclusively, of immunological analyses to measure the immunogenicity of candidate vaccines that are evaluated in clinical vaccine trials conducted in CEVAC’s Clinical Unit or elsewhere. The Core Lab not only executes but also develops, qualifies and validates immunologic readouts that meet the requirements of the sponsor. CEVAC Core Lab team consists of 12 skilled and dedicated staff members. General coordination is in the hands of Mr. F. Clement and Mrs. G. Waerlop takes care of IMI project management.New Publications produced by BIOVACSAFE ProjectDevelopment of a custom pentaplex sandwich immunoassay using Protein-G coupled beads for the Luminex xMAP platform
McDonald J.U., Ekeruche-Makinde J., Ho M.M., Tregoning J.S., Ashiru O.
J Immunol Methods. 433:6-16. 2016
Multiplex bead-based assays have many advantages over ELISA, particularly for the analyses of large quantities of samples and/or precious samples of limited volume. Although many commercial arrays covering multitudes of biologically significant analytes are available, occasionally the development of custom arrays is necessary. Here, the development of a custom pentaplex sandwich immunoassay using Protein G-coupled beads, for analysis using the Luminex® xMAP® platform, is described. This array was required for the measurement of candidate biomarkers of vaccine safety in small volumes of mouse sera. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in HumansSpensieri F., Siena E., Borgogni E., Zedda L., Cantisani R., Chiappini N., Schiavetti F., Rosa D., Castellino F., Montomoli E., Bodinham C.L., Lewis D.J., Medini D., Bertholet S., Del Giudice G.Plos ONE. 11(6):e0157066. 2016 CD4+ T follicular helper cells (TFH) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4+IL-21+ICOS1+ T helper (TH) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59®-adjuvanted TIIV (ATIIV), or saline placebo.Upcoming eventsUpcoming interesting CONFERENCES are:5-9th February 2017, Keystone Symposia on Molecular and Cellular Biology: Microbiome in Health and Disease (J8). Keystone, Colorado, USA
16–17th February 2017, ICI 2017: 19th International Conference on Immunology. London, United Kingdom19th – 23rd February 2017, Keystone Symposia: Viral Immunity – Mechanisms and Consequences. Santa Fe, New Mexico, USA 21st-22th February 2017,12th Annual Biomarkers Congress. Manchester, UK
15–18th March 2017, 11th World Immune Regulation Meeting. Davos, Switzerland
26-30th March 2017, Keystone Symposia:HIV Vaccines. Steamboat Springs, Colorado, USA10–12th April 2017, World Vaccine Congress Washington 2017. Washington D.C., USA19th-21st April 2017, Influenza Vaccines For The World. Lausanne, Switzerland23rd-27th April 2017, Keystone Symposia: B Cells and T Follicular Helper Cells – Controlling Long-Lived Immunity. British Columbia, Canada24-26th April 2017, 20th Annual Conference on Vaccine Research. Bethesda, MD1st– 4th May 2017, Keystone Symposia: Modeling Viral Infections and Immunity. Estes Park, Colorado, USA Upcoming interesting COURSES are:8-19th May 2017, ADVAC- Advanced Course of Vaccinology. Veyrier-du-Lac (French Alps), Geneva, Switzerland BioVacSafe PublicationsList of publications acknowledging BioVacSafe are:Development of a custom pentaplex sandwich immunoassay using Protein-G coupled beads for the Luminex xMAP platform McDonald J.U., Ekeruche-Makinde J., Ho M.M., Tregoning J.S., Ashiru O. J Immunol Methods. 2016 Jun;433:6-16. doi: 10.1016/j.jim.2016.02.018Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans Spensieri F., Siena E., Borgogni E., Zedda L., Cantisani R., Chiappini N., Schiavetti F., Rosa D., Castellino F., Montomoli E., Bodinham C.L., Lewis D.J., Medini D., Bertholet S., Del Giudice G. Plos ONE, 2016 11(6):e0157066. doi: 10.1371/journal.pone.0157066Reprogramming the T cell response to tuberculosis Woodworth J.S. and Andersen P. Trends Immunol., 2016 37(2):81-3. doi:10.1016/j.it.2015.12.009Interferon-γ from brain leukocytes enhances meningitis by Type 4 Streptococcus pneumoniae Pettini E., Fiorino F., Cuppone A.M., Iannelli F., Medaglini D., Pozzi G. Front Microbiol., 2015 6:1340.doi:10.3389/fmicb.2015.01340Epigenetics and proteomics join transcriptomics in the quest for tuberculosis biomarkers Esterhuyse M.M., Weiner J. 3rd, Caron E., Loxton A.G., Iannaccone M., Wagman C., Saikali P., Stanley K., Wolski W.E., Mollenkopf H.J., Schick M., Aebersold R., Linhart H., Walzl G., Kaufmann S.H.MBio., 2015 6(5):e01187-15. doi: 10.1128/ mBio.01187-15Partial attenuation of RSV with a deletion of the SH gene is associated with elevated IL-1B Russell R.F., McDonald J.U., Ivanova M., Zhong Z., Bukreyev A., Tregoning J.S. Journal of Virology, 2015 89(17):8974-81. doi: 10.1128/JVI.01070-15Evaluating the efficiency of isotope transmission for improved panel design and a comparison of the detection sensitivities of mass cytometer instruments Tricot S., Meyrand M., Sammicheli C., Elhmouzi-Younes J., Corneau A., Bertholet S., Malissen M., Le Grand R., Nuti S., Luche H., Cosma A. Cytometry A., 2015 87(4):357-68. doi: 10.1002/cyto.a.22648The human immune response to tuberculosis and its treatment: a view from the blood Cliff J.M., Kaufmann S.H.E., McShane H., van Helden P., O’Garra A.
Immunological Reviews, 2015 264(1):88-102.doi:10.1111/imr.12269Vaccines, new opportunities for a new society Rappuoli R., Pizza M., Del Giudice G., De Gregorio E. Proc Natl Acad Sci U S A., 2014 111(34):12288-93. doi:10.1073/ pnas.140298111Toward a unified biosignature for tuberculosis Maertzdorf J., Kaufmann S.H., Weiner J. 3rd. Cold Spring Harb Perspect Med., 2014 pii:a018531.doi:10.1101/ cshperspect.a018531Novel vaccination strategies against tuberculosis Andersen P. and Kaufmann S.H.E. Cold Spring Harb Perspect Med, 2014 doi:10.1101/cshperspect.a018523.4(6): a018523 Challenges and responses in human vaccine development Kaufmann S.H.E , Mc Elrath M.J., Lewis D.J.M., Del Giudice G. Curr. Opin. Immunol, 2014 doi:10.1016/ j.coi.2014.01.009Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease Dorhoi A., Iannaccone M., Maertzdorf J., Nouailles G., Weiner J. 3rd, Kaufmann S.H.E. Frontiers in Immunol., 2014 doi:10.3389/fimmu.2014.00036Tuberculosis vaccine development at a divide Kaufmann S.H.E Curr Opin Pulm Med., 2014 20(3):294-300. doi:10.1097/ MCP.0000000000000041Progress in tuberculosis vaccine development and host-directed therapies—a state of the art review Kaufmann, S.H.E., Lange C., Rao M., Balaji K.N., Lotze M., Schito M., Zumla A.I., Maeurer M. Lancet Respir Med., 2014 2(4):301 -20. doi: 10.1016/S2213-2600 (14)70033-5Recent advances towards tuberculosis control: vaccines and Biomarkers Weiner J. 3rd & Kaufmann S.H.E. J Intern Med, 2014 275(5):467-80. doi:10.1111/ joim.12212TRANSVAC workshop on standardisation and harmonisation of analytical platforms for HIV, TB and malaria vaccines: ‘How can big data help?’ Dutruel C., Thole J., Geels M., Mollenkopf H.J., Ottenhoff T., Guzman C.A., Fletcher H.A., Leroy O., Kaufmann S.H. Vaccine, 2014 32(35):4365-8. doi: 10.1016/j.vaccine.2014.06.014Standardization and simplification of vaccination records Maurer W., Seeber L., Rundblad G., Kochhar S., Trusko B., Kisler B., Kush R., Rath B. Expert Review of Vaccines, 2014 13(4):545-59. doi:10.1586/14760584. 2014.892833The dual role of biomarkers for understanding basic principles and devising novel intervention strategies in tuberculosis Weiner J. 3rd, Maertzdorf J., Kaufmann S.H. Ann N Y Acad Sci., 2013 1283:22-9.doi:10.1111/j.1749-6632.2012. 06802.xOMIP-016: Characterization of antigen-responsive macaque and human T– cells Guenounou S., Bosquet N., Dembek C.J., Le Grand R., Cosma A. CytometryPART A, 2013 83(2):182-4. doi: 10.1002/cyto.a.22233Tuberculosis vaccines: time to think about the next generation Kaufmann S.H.E. Seminars in Immunology, 2013 25:172-181. doi:10.1016/j.smim.2013.04.006Defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse mode Everitt A. R., Clare S., McDonald J.U., Kane L., Harcourt K., Ahras M., Lall A., Hale C., Rodgers A., Young D. B., Haque A., Billker O., Tregoning J. S., Dougan G., Kellam P. Plos one, 2013 8(11):e80723.doi:10.1371/journal.pone. 0080723Inflammation in tuberculosis: interactions, imbalances and interventions
Kaufmann S.H.E. and Dorhoi A. Curr. Opin. Immunol., 2013 25: 441–449. doi:10.1016 /j.coi.2013.05.005Enabling biomarkers for tuberculosis control Maertzdorf J., Weiner J. 3rd, Kaufmann S.H.E. Int J Tuberc Lung Dis., 2012 16(9):1140-8. doi:10.5588/ijtld.12. 0246Tuberculosis vaccine development: strength lies in tenacity Kaufmann S.H.E. Trends in Immunol., 2012 33(7):373-9. doi:10.1016/j.it.2012 .03.004BIOVACSAFE contactsBIOVACSAFE_ProjectManagement@surrey.ac.uk – http://www.biovacsafe.eu This project is supported by the grant n° 115308 from the Innovative Medicines Initiative JU, a joint undertaking between the European Union and the EFPIA companies’ in kind contribution.