BioVacSafe – Newsletter  July 2014 Issue number 4 Project news – BioVacSafe 2nd Annual MeetingThe BioVacSafe annual meeting was hold on 20-21 March 2014 in Siena.  All partners of the project were invited for this meeting. More than 80  participants attended  to present and discuss the results of the second year of research.Here you can find the Proceedings of the annual meetingBioVacSafe Partners ProfileIn every biannual newsletter the profile of some of BioVacSafe’s research partners is highlighted.In this edition you will meet the Immunoarray Ltd in Rehovot, Israel; the Imperial College London in London, UK and GlaxoSmithKline in Namur Area, Belgium.   Immunarray LtdFounded in 2006, Immunarray Ltd. holds an exclusive, worldwide license from the Weizmann Institute of Science for the iCHIP™ technology which was conceived and developed by Prof. Irun Cohen. ImmunArray is dedicated to the development of antigen microarray technology for profiling the repertoire of circulating antibodies in patients and it is currently developing iCHIP™ -based tests for autoimmune diseases (early diagnosis, prognosis, monitoring response to treatment); for allograft patients (predicting and monitoring acute and chronic rejection); for drug development and for vaccination safety. The company has assembled a distinguished group of world-renowned advisors and partners and employs a multi-disciplinary team to cover all areas required to develop the antigen microarray technology and its diagnostic products: immunology, bio-informatics, complex systems, bio-physics and microarray printing technology. ImmunArray boasts a seasoned management team with a solid track record in launching early-stage biotechnology and diagnostics companies. Prof. Irun Cohen and IA membersThe iCHIPTM technology is based on an antigen microarray and a bioinformatics analysis system that enables profiling the antibody repertoire expressed against numerous selected antigen molecules simultaneously. ImmunArray’s profiling generates immune system signatures; these signatures reveal the individual’s state of health or disease. In the current version of the iCHIPTM, 10 microliters of patient serum, plasma or other body fluid can be tested to measure over 2,000 antibody reactivities to different proteins, peptides, carbohydrates, lipids, and nucleic acids. These informative target molecules represent a variety of biological processes including: immune system regulation and activity, stress proteins, structural molecules, apoptosis, growth and differentiation, neuro-endocrine, vascular and adhesion molecules and more. Based on the initial profiles, a smaller subset of antigens can be identified for placement on an individual iCHIPTM for a given indication.  Imperial College LondonThe team at Imperial College London is headed up by Prof Robin Shattock and is involved in the animal studies (WP2) component of the Biovacsafe Project, which Prof Shattock co-chairs. The studies have been designed to reflect the clinical trials and allow us to further refine the novel biomarkers identified in the human studies for future studies. They will also allow integration of pre-clinical studies for future vaccine development. Dr Paul McKay’s group performing a series of studies to determine commonalities and differences in biomarker expression across commonly used animal-platforms for preclinical toxicology (mice, rats and rabbits). These studies are designed to mirror those performed in the clinical studies under Work package 1 and involve collecting RNA for microarray analysis by the team at MPIIB from blood, muscle and lymph node biopsies taken at the same time points as the human study. The vaccines are being compared to known inflammatory stimuli (LPS, incomplete Freund’s adjuvant and Poly I:C) which provide the top thresholds for the studies. The samples from the mouse studies are currently being collected and will soon be shipped for the detailed microarray analysis at MPIIB. Data from these studies will be directly comparable to those performed in the matched clinical studies. The mouse model was used first because of the greater availability of microarray reagents and the rat and rabbit studies will begin when the data from the mouse genome microarrays have been analyzed and used to focus the range of biomarkers to be assessed in the rat and rabbit models. These studies will enable the integration of mouse and human genomic data and validation of identified vaccine safety biomarkers in a further two species. The outputs of this component of the project will be a list of the biomarkers of vaccine safety in mouse (the main experimental model for vaccine development) and rats/rabbits (the main animal models used for toxicology screening). Dr John Tregoning’s group is exploring the different responses to vaccination at the extremes of age, using neonatal, adult and elderly mice. The different aged mice are vaccinated with influenza vaccine, with and without adjuvant. Blood samples have been collected at the same time points as the human influenza vaccine clinical trial and are being analyzed by luminex for a large panel of inflammatory markers. To explore the upper limits of inflammatory responses, vaccine responses are being compared to the responses to influenza infection in animals at different ages. The samples have all been collected and we are currently developing an in house luminex assay to mirror the clinical panel. We have also developed influenza infection models with pandemic H1N1, H3N2 and influenza B viruses and these are being used to further assess induction of inflammatory markers relative to vaccine-induced responses. These will be compared to responses to infection (homologous and heterologous) in vaccine-primed animals. These studies will be compared and cross-validated with data generated in the human clinical studies with the aim of selecting relevant biomarkers that may be predictive of response not only in adults, but also neonatal and elderly cohorts. Prof. Robin Shattock and Dr John Tregoning Dr Paul McKay  Imperial College London is a science based university with an international reputation for excellence in teaching and research, rated as the world’s tenth best university in the Times Higher Education World University Rankings 2013. Imperial College has an annual research spend of £60M with a cohort of around 400 PhD students and an extensive teaching programme. The component work of BioVacSafe will be carried out in a suite of newly refurbished laboratories as part of the Section of Virology in the Faculty of Medicine at the St Mary’s Campus in Paddington, London. These facilities contain state of the art equipment for the analysis of immune responses to vaccination and infection.  GlaxoSmithKlineGSK – who are we?GSK is a science-led global healthcare company. Our mission is to improve the quality of human life by enabling people to do more, feel better and live longer. We research, manufacture and make available products and solutions in pharmaceuticals, vaccines and consumer healthcare. In 2013, the vaccines business represented 13% of the overall turnover of GSK1. Vaccines marketed for pediatric use include vaccines against: polio, diphtheria, tetanus, pertussis, measles, mumps, rubella, meningitis C, chicken pox, pneumococcal disease and rotavirus infection. GSK also markets adolescent, adult and travel vaccines. These include vaccines against: flu (pandemic and seasonal), human, papilloma virus (cervical cancer), hepatitis A and B, typhoid, meningitis A,C,W,Y, and booster  vaccines against diphtheria, tetanus, pertussis and polio. During 2013, GSK distributed over 860 million doses of vaccines in 170 countries, of which 80% were in developing countries1. In its Global Vaccine Action Plan from 2011-2020, the WHO predicts that widening access to vaccines could prevent between 24.6 – 25.8 million deaths by the end of the decade2. The company has dedicated research programmes for diseases that affect the developing world. We are one of the few healthcare companies researching new vaccines for all three of the World Health Organization’s priority diseases: HIV/AIDS, malaria and tuberculosis. At GSK, we are committed to making our vaccines available to as many people as possible. We introduced a tiered pricing policy to make vaccines affordable in low-income countries, a global manufacturing network and partnerships that span the development of vaccines to their distribution across the world.Our approach to Research and DevelopmentThe company has a long heritage of partnerships and collaborative ventures with over 100 R&D collaborations currently on-going. A key part of GSK’s approach in vaccines R&D is expanding its access to new vaccine technologies. In order drive innovation, we aim to bring together the best science has to offer by working alongside external partners. We form collaborations with large pharmaceutical companies, small biotech businesses, consortia, charities and academia (including graduate and post-doctoral research programs). These encompass multi-disciplinary approaches such as working with the European Framework Programs and Innovative Medicines Initiative (IMI). All serve to inform different phases of R&D. Areas of interest for potential partnerships with GSKFundamental and applied immunologyUnderstanding host-pathogen interactions, understanding immune responses to infectious diseases and vaccines, and developing new protective antigensNew vaccine targetsDiscovering targets for infectious diseases (e.g. nosocomial diseases and diseases prevalent in the developing world) and non-infectious diseases (e.g. neurological degenerative diseases, autoimmune diseases and cancers)AdjuvantsDeveloping new approaches to modulate the immune system and understanding the mode of action of adjuvantsAntigen deliveryDeveloping nanoparticles and virus-like particles, and investigating antigen stability.Live viral and bacterial vectorsVaccine deliveryDeveloping mucosal, oral, sublingual, nasal and intradermal delivery methodsNew assessment technologies and analytical toolsMiniaturizing clinical assays, developing quality-assurance assays and biomarkers, and applying systems biology to (new) readoutsNew production process technologiesAll aspectsContact: vaccinespartnering@gsk.com Meeting people’s needsVaccines are one of the most effective solutions in preventing disease. Every year, vaccines prevent up to 3 million deaths and save 750,000 children from disability 3.GSK carries out early stage research and later stage development. The company currently has 16 vaccines in development. We use adjuvants to improve the immune system’s response to antigens contained in vaccines and we have been innovating in the area of adjuvant systems for more than 20 years. We are engaged in a continued search to develop innovative vaccines for the benefit of those people who need them. Our commitment to safetyAs part of our commitment to safety, GSK manufactures its vaccines to the highest possible quality standards across the world, in state-of-the-art facilities, and carefully monitors their impact and effectiveness. This is illustrated by the fact that 520 quality tests applied before a dose of pneumococcal vaccine is shipped.GSK supports the aim of the IMI-funded BioVacSafe project to develop cutting edge tools to speed up and improve the testing and monitoring of vaccine safety, both before and after release to the market. We make our contribution by partnering with other European vaccine development and manufacture companies as well as top experts from academic institutions and small and medium-sized enterprises (SMEs). We support the BioVacSafe project by sharing our expertise and experience mostly on clinical study design and preclinical models with the consortium partners.It is hoped that the project will ultimately accelerate the development and introduction of a new generation of safer, more effective vaccines.The GSK representative is Philippe Denoël (philippe.denoel@gsk.com). 2013 GSK Annual Report. Published February 2014WHO Global Vaccine Action Plan 2011 – 2020Ereth, J. Vaccine 2003;21:4111  Upcoming events:Upcoming interesting conferences are:  4th International Conference on Vaccines & Vaccination OMICS group, September 24-26, 2014 Valencia, Spain.  More information can be found hereThe Modes of Action of Vaccine Adjuvant October 8-13, 2014 Sheraton Seattle Hotel, Seattle, Washington, USA. More information can be found here World Vaccine Congress 2014 22-23 October 2014, Lille grand Palais, Lille, France. More information can be found here 8th Vaccine & ISV Congress 26-28 October 2014 | Philadelphia, PA, USA. More information can be found here click here to find the program Recent Pubblications:A list of recent publications related to BioVacSafe project:Kaufmann, 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. 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/24950356Weiner J 3rd, Maertzdorf J, Kaufmann SH. The dual role of biomarkers for understanding basic principles and devising novel intervention strategies in tuberculosis. Ann N Y Acad Sci. 2013; 1283: 22-29. http://www.ncbi.nlm.nih.gov/pubmed/23181737Guenounou S, Bosquet N, Dembek CJ, Le Grand R, Cosma A. OMIP-016: Characterization of Antigen-Responsive Macaque and Human T –cells. Cytometry PART A 2013; 83A: 182-184. http://onlinelibrary.wiley.com/doi/10.1002/cyto.a.22233/abstractKaufmann, S. Tuberculosis vaccines: Time to think about the next generation. Seminars in Immunology, 2013; 25: 172-181. http://www.sciencedirect.com/science/article/pii/S1044532313000225A. R. Everitt, S. Clare, J. U. McDonald,, L.Kane, K.Harcourt, M. Ahras, A. Lall, C.Hale, A. Rodgers, D. B. Young, A. Haque, O. Billker, J. S. Tregoning, G. Dougan, P. Kellam: Defining the range of pathogens susceptible to ifitm3 restriction using a knockout mouse mode. Plos one 2013; 8: 1- 12. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0080723Kaufmann, S.H.E., A. Dorhoi: Inflammation in tuberculosis: interactions, imbalances and interventions. (Special issue: Host pathogens). Curr. Opin. Immunol. 2013; 25: 441–449. http://www.sciencedirect.com/science/article/pii/S0952791513000757Maertzdorf J, Weiner J 3rd, Kaufmann SH. Enabling biomarkers for tuberculosis control. Int J Tuberc Lung Dis. 2012;16(9):1140-8. http://www.ncbi.nlm.nih.gov/pubmed/22871324Kaufmann, S. Tuberculosis vaccine development: strength lies in tenacity. Trends in Immunol. 2012; 33 (7):373-379. http://www.ncbi.nlm.nih.gov/pubmed/22560865 BioVacSafe 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.