BioVacSafe – Newsletter July  2015 Issue number 6   BioVacSafe Third Annual Meeting  The third BioVacSafe annual meeting was hold on 18th – 20th March 2015 in Ghent, Belgium.  All partners of the project were invited for this meeting. More than 70  participants attended  to present and share the results of the last year of research (by invitation only).Here you can find the Proceedings of the annual meeting Subscribe to this newsletterBioVacSafe Partners ProfileIn every biannual newsletter the profile of some  of BioVacSafe’s research partners is highlighted. In this edition you will meet the  Max Planck Institute for Infection Biology (MPIIB) in Berlin, Germany, St George’s University of London in London, UK  and deCODE genetics in Reykjavik, Iceland.    Max Planck Institute for Infection BiologyThe Max Planck Institute for Infection Biology (MPIIB), one of the Max Planck Society’s more than 80 institutes, is among Europe’s centres of excellence committed to biological research in the field of infectious diseases. Within the BioVacSafe project, MPIIB is involved in WPs 1 and 2, working in close harmony with partners and providing advice on setting up experimental protocols for clinical and animal studies. Its main effort, however, is within WP 7, the project’s Technology Core wherein transcriptomic and cytokine/chemokine profiles are being generated from blood samples obtained within clinical and animal studies. Transcriptional profiling and functional genomics provide an excellent basis for detailed analyses of host responses to immunization. These measurements will not only support and facilitate vaccine safety testing, but also provide vital information about gene products and their respective metabolic pathways that serve as potential targets for novel intervention strategies. We envisage that these transcriptomic analyses will aid the design of new and safe vaccines, and stimulate optimal vaccine-induced memory and effector functions, to fend off infectious diseases of major relevance. So far, MPIIB has generated transcriptomic profiles from ~2,200 human and animal samples within the BioVacSafe project and over 1,600 cytokine/chemokine profiles. Our work within the Technology Core also includes computational analysis of the transcriptomic profiles generated within the BioVacSafe project. Combining datasets from the different trials and cross-experimental analyses provide some of the main challenges within the project. Towards the end of the BioVacSafe project, in-house bioinformatics expertise will be harnessed for an integrative evaluation of analysis platforms, combining gene expression, metabolic networks and cytokine/chemokine responses. MPIIB’s BIOVACSAFE biomarker profiling team: from left-to-right: Jeroen Maertzdorf, Gayle McEwen, Robert Golinski, January Weiner, Karin Hahnke, Stefan H.E. Kaufmann. Not in the picture: Sandra Leitner, Ina Wagner, Hans Mollenkopf. The Max Planck Institute for Infection Biology is situated in the heart of Berlin on the historical Charité medical campus, where Robert Koch and Emil Behring made their important discoveries, establishing the field of infection and vaccine research, and in close proximity to the Parliament house and main government offices. Infectious diseases continue to be the number one cause of death worldwide. Nearly one third of deaths caused by infectious diseases are attributable to “the big three”, namely AIDS, malaria and tuberculosis (TB). The MPIIB employs multidisciplinary approaches to infection biology, comprising concepts and methodologies of molecular genetics, immunology, cell biology, epidemiology, clinical research and protein chemistry. The Institute promotes research that paves the way for the design of rational measures of control of infectious diseases. Notably, the MPIIB fosters modern vaccination approaches and rational biosignature design. Research topics of the MPIIB focus on mechanisms underlying infectious diseases. The Department of Immunology, headed by Stefan H.E. Kaufmann, focuses on analyses of the immune response to TB with the aim of developing better intervention measures. One of its major goals is the development of an effective vaccine against TB disease and the design of biosignatures for disease diagnosis and prognosis.   St George’s University of LondonSt George’s, University of London (SGUL) has its origins in 1733, it’s the UK’s only university dedicated to medical and health sciences education, training and research; The team at St George’s University of London is headed by Professor Philip Cooper and is involved in human studies addressing the effects of widely used childhood vaccines on the risk of autoimmunity and allergic reactions. The studies are based in pediatric populations in coastal Ecuador. Within the BioVacSafe project, SGUL group has been looking at the effects of a dT booster in schoolchildren on the development of de novo autoantibodies after vaccination in children associated with post-vaccination fever (work-package 3), in collaboration with Dr Irun Cohen’s team (BioVacSafe partner, ImmunArray Ltd) who have developed a chip to detect a wide repertoire of autoantibodies. This study aims to investigate whether AEFIs such as fever may be associated with the development of autoantibodies predictive of future autoimmune disease.  BioVacSafe study team at clinic in coastal Ecuador. Left to right: Xavier Suarez, Natalya Chugcho, Sofia Loor, Adriana Zambrano, Maritza Vaca, Araceli Falcones, Martha Chico, and Carlos Sandoval Within work-package 4, we have been using a population-based birth cohort, the ECUAVIDA cohort, being followed up to 8 years of age in a rural District in Esmeraldas Province, Ecuador, to look at the temporal association between routine childhood immunizations and the development of allergic conditions during childhood, specifically wheeze and allergic skin conditions.    The clinic at the District Hospital in Esmeraldas Province used for follow-up of the ECUAVIDA cohort The increase in the incidence of Pertussis disease worldwide has been attributed to less effective long-term immunity associated with acellular vaccines. Whole cell vaccines – that have gradually been replaced by acellular vaccines in many regions of the World since the 1990s – were associated with a high incidence of inflammatory adverse events. There are limited data on of potential mechanisms that underlie the host inflammatory response to whole cell Pertussis vaccines. A better understanding of these mechanisms will inform the development of a new generation of Pertussis vaccines designed to provide long-lasting immunity without immunization associated adverse effects, The SGUL team is now looking at the reactogenicity of DPT vaccines containing whole cell Pertussis, that are used by the Ministry of Public Health in Ecuador as part of the routine immunization schedule in infants, and will be looking at changes in gene expression and inflammatory biomarker profiles associate with adverse events (i.e. fever) following immunization with the aim of identifying biomarkers that are predictive of such adverse events following immunization. This work will be done collaboration with Professor Stefan Kauffman’ s team (BioVacSafe partner, MPIIB, Berlin) and will be done in parallel with detailed studies in animal models vaccinated with the same vaccine done by Professor Robin Shattock’s team (BioVacSafe partner, Imperial College, London) . deCODE geneticsdeCODE genetics (Islensk Erfdagreining ehf) is an Icelandic research company of about 170 employees and a global leader in analyzing and understanding the human genome. The main objective of deCODE’s research is to shed a light on the underlying biological pathways of human nature and since the founding of the company in 1996, deCODE has been focused on analysing how variations in the sequence of the human genome can translate into variations in observable human traits. Prof. Ingileif JonsdottirdeCODE’s research within BioVacSafe is led by prof. Ingileif Jonsdottir. It focuses on the relationship between immune mediated adverse events (AE); autoimmune diseases and sequence variants in the human genome, taking advantage of genetic data generated from the deCODE’s whole genome sequencing project, with 28.3 million sequence variants identified through whole-genome sequencing of over 10,000 Icelanders imputed into 155,000 chip-typed indviduals and their relatives. These include individuals that have experienced immune mediated AE following smallpox vaccination or influenza infection, anaphylaxis, have narcolepsy or autoimmune disease (AID). Sequence variants found to associate with immune mediated AE will be validated in foreign sample sets generated through BioVacSafe studies or available at deCODE through other international collaboration. Coding sequence variants that associate with immune mediated AE are characterized with respect to their functional effects on the encoded protein and intronic, intragenic and regulatory region variants tested in silico for effects on gene expression using deCODE‘s Genetics of Gene Expression Database. In BioVacSafe deCODE also studies the prevalence of autoimmune diseases in adults, using its clinical database, that includes over 14,000 patients with various AIDs, and assesses the relationship between susceptibility to chronic infection and AID by determining AID prevalence among individuals that have or have not had tuberculosis or M. tuberculosis infection.  Through its whole genome sequencing effort deCODE has discovered many rate sequence variants that confer high risk to disease, including various cancers, cardiovascular, neurological, phsyciatric, autoimmune and inflammatory diseases. Over 400 peer reviewed publications have resulted from deCODE’s genetic research programmes, both internal research and collaborative programmes. deCODE’s research was recently featured in an issue of Nature genetics, including 4 original papers describing deCODE’s discoveries and an editorial, “Letters from Iceland“. deCODE has extensive experience with EU research programs, having participated in over 50 projects under the 6th and 7th Framework Programmes, IMI and Horizon 2020 collaborative projects, of which 25 are currently on-going. deCODE is an Icelandic legal entity, fully owned subsidiary of the pharmaceutical company Amgen Inc. since December 2012. deCODE’s headquarters are a located in a recently constructed 15,000 m2 building in central Reykjavik, Iceland; with state-of-the art IT systems for storing deCODE’s unique genetic-, phenotypic- and geneology data resource, coupled with a  high performance CPU cluster for in depth statistical analyses.In the gene discovery work, deCODE has gathered genotypic and medical data from more than 155,000 volunteer participants, comprising well over half of the adult population in Iceland. Using Iceland’s uniquely comprehensive genealogical records, deCODE has also put together a genealogy database covering the entire present day population and stretching back to the founding of the country more than 1000 years ago. The combination of size and structure of the Icelandic population, the generous participation of so many people in our discovery work, the comprehensive genealogy, and high quality universal healthcare in Iceland make possible very large-scale studies of unprecedented power of virtually any common disease – or human trait.  deCODE’s biobank is equipped with an automatic robotic freezer, storing more than 500,000 blood vacutainers. The deCODE biobank has a biosafety level II tissue/cell culture laboratory and deCODE operates one of the highest throughput genotyping- and whole genome sequencing laboratories in the world, where all sample processing controlled and monitored through deCODE’s Laboratory Information Management System (LIMS) for safe- and efficient, sample tracking, access- and process control etc.Upcoming events:Upcoming interesting conferences are: 6th Euro Global Summit and Expo on Vaccines & Vaccination 17-19 August 2015, Birmingham, UK. More information can be found here 4th European Congress of Immunology 6 – 9 September 2015, Vienna, Austria. More information can be found here9th European Congress on Tropical Medicine and International Health  6 – 10 September 2015, Basel, Switzerland. More information can be found hereICI 2015 : 17th International Conference on Immunology 25 -26 September 2015, London, UK. More information can be found hereInfluenza Vaccines for the World 6 – 9 October 2015, Albufeira, Portugal. More information can be found hereKeystone symposium on “Systems Immunology: From Molecular Networks to Human Biology” 10 -14 January 2016, Big Sky Resort, Big Sky, Montana, USA. More information can be found hereMore interesting meetings in the field of immunology here Recent Pubblications:A list of recent publications related to BioVacSafe project:  Jacqueline M. Cliff J.M., Kaufmann S.H.E., McShane H, van Helden P., O’Garra A. The human immune response to tuberculosis and its treatment: a view from the blood. Immunological Reviews, 2015; 264 (1): 88-102. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368415/Rappuoli R, Pizza M, Del Giudice G, De Gregorio E:Vaccines, new opportunities for a new society. Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12288-93. doi: 10.1073/pnas.140298111. http://www.ncbi.nlm.nih.gov/pubmed/25136130Maertzdorf J, Kaufmann SH, Weiner J 3rd. Toward a unified biosignature for tuberculosis. Cold Spring Harb Perspect Med. 2014 Oct 23. pii: a018531. doi: 10.1101/cshperspect.a018531. http://www.ncbi.nlm.nih.gov/pubmed/25342061Andersen P and Kaufmann S.H.E. Novel vaccination strategies against tuberculosis. . doi:10.1101/cshperspect.a018523.4(6): a018523 http://perspectivesinmedicine.cshlp.org/content/4/6/a018523.full#content-blockKaufmann S.H.E , Mc Elrath MJ, Lewis DJM, Del Giudice G: Challenges and responses in human vaccine development. Curr. Opin. Immunol 2014; 28:18-26. http://www.sciencedirect.com/science/article/pii/S0952791514000107Dorhoi A., Iannaccone M., Maertzdorf J., Nouailles G., Weiner J. 3rd, Kaufmann S.H.E.:Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease. Frontiers in Immunol 2014; 5(36): 1-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913996/Kaufmann, S.H.E: Tuberculosis vaccine development at a divide. Curr Opin Pulm Med 2014, 20:294–300. http://www.ncbi.nlm.nih.gov/pubmed/24626237Kaufmann, S.H.E.,Lange C., Rao M., Balaji K.N., Lotze M., Schito M., Zumla A.I., Maeurer M.: Progress in tuberculosis vaccine development and host-directed therapies—a state of the art review. Lancet Respir Med 2014; 2: 301–20. . http://www.sciencedirect.com/science/article/pii/S2213260014700335Weiner J. 3rd & Kaufmann S.H.E:Recent advances towards tuberculosis control: vaccines and Biomarkers. Vaccine.J Intern Med, 2014, 275; 467–480. http://www.ncbi.nlm.nih.gov/pubmed/24635488Dutruel C, Thole J, Geels M, Mollenkopf HJ, Ottenhoff T, Guzman CA, Fletcher HA, Leroy O, Kaufmann SH:TRANSVAC workshop on standardisation and harmonisation of analytical platforms for HIV, TB and malaria vaccines: ‘How can big data help?’. Vaccine. 2014 Jun 17. pii: S0264-410X(14)00803-2. http://www.ncbi.nlm.nih.gov/pubmed/24950356Maurer W, Seeber L, Rundblad G, Kochhar S, Trusko B, Kisler B, Kush R, Rath B; Vienna Vaccine Safety Initiative: Standardization and Simplification of Vaccination Records. Expert Review of Vaccines 2014, Apr;13(4):545-59. http://www.ncbi.nlm.nih.gov/pubmed/24597495BioVacSafe contacts:info@biovacsafe.eu – http://www.biovacsafe.eu – Facebook – Twitter – Linkedin 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.