Vaccines-2013 - OMICS Group

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Esma S. Yolcu, J Vaccines Vaccin 2013, 4:5http://dx.doi.org/10.4172/2157-7560.S1.0163 rd International Conference onVaccines & VaccinationJuly 29-31, 2013 Embassy Suites Las Vegas, NV, USANegative vaccination with donor splenocytes engineered with FasL as an effective mean ofinducing transplantation toleranceEsma S. YolcuUniversity of Louisville, USAFasL is a member of TNF ligand superfamily and plays an essential role in immune homeostasis. This critical role played byFasL renders this molecule as an attractive target for immunomodulation to achieve tolerance to auto and transplantationantigens. Immunomodulation of immune system with genetically modified cells expressing FasL was shown to induce toleranceto alloantigens. However, genetic modification of primary cells in a rapid, efficient, and clinically applicable manner provedchallenging. Therefore, we developed a protein display technology that allows efficient engineering of donor splenocytes witha novel form of FasL protein (SA-FasL) and tested the efficacy of engineered cells as a negative vaccination strategy to inducetolerance to cardiac allografts. Intraperitoneal injection of ACI rats with WF splenocytes displaying SA-FasL on their surfaceresulted in tolerance to donor, but not F344 third party, cardiac allografts. Tolerance was associated with apoptosis of donorreactive T effector cells and induction/expansion of CD4+CD25+FoxP3+ T regulatory (Treg) cells. Treg cells played a criticalrole in the observed tolerance as adoptive transfer of sorted Treg cells from long-term graft recipients into naïve unmanipulatedACI rats resulted in indefinite survival of secondary WF grafts. Immunomodulation with allogeneic cells rapidly and efficientlyengineered to display on their surface SA-FasL protein provides an effective and clinically applicable means of cell-based therapywith potential applications to regenerative medicine, transplantation, and autoimmunity.BiographyEsma S. Yolcu is Assistant Professor of Microbiology and Immunology and the Director of Imaging Facility at the Institute for Cellular Therapeuticsand member of James Brown Cancer Center, University of Louisville, Louisville, KY. She received her Ph.D. degree from University of Ankara,Ankara, Turkey and joined the University Of Louisville School Of Medicine in Louisville, KY, to pursue her postdoctoral training. Dr. Yolcu’s researchfocuses on novel immunomodulatory approaches for the induction of tolerance to auto and alloantigens for the purpose of treating rejection andautoimmunty. She is the recipient of several awards, member of various national and international societies, serves on Editorial Board of scientifi cjournals, and published over 67 peer-reviewed papers, abstracts, and review articles in high ranking journals, such as Immunity, Circulation, Blood,and the Journal of Immunology.esma.yolcu@louisville.eduJ Vaccines Vaccin 2013ISSN: 2157-7560, JVV an open access journalVaccines-2013July 29-31, 2013Volume 4 Issue 5Page 42
Campbell Bunce, J Vaccines Vaccin 2013, 4:5http://dx.doi.org/10.4172/2157-7560.S1.0163 rd International Conference onVaccines & VaccinationJuly 29-31, 2013 Embassy Suites Las Vegas, NV, USADesign and clinical evaluation of a novel self-adjuvanting peptide-based pan influenza AT-cell vaccineCampbell BunceImmune Targeting Systems Ltd, UKImmune Targeting Systems (ITS) has developed a rationally designed, safe, self-adjuvanting vaccine technology that inducesrobust cell mediated immune (CMI) responses to peptide antigens. The vaccine concept is based on linking a fluorocarbonchain to long immunogenic peptides. These ‘fluoropeptides’ bearing specific physico-chemical properties spontaneously formmicelles in solution and enhance immunogenicity by the formation of an in vivo short-term depot thereby allowing efficientexposure of peptide antigens to the immune system.ITS’ has applied this Depovaccine technology to its lead programme Flunisyn, an influenza T cell vaccine designed totarget all seasonal and pandemic strains of influenza A. Flunisyn consists of 6 fluoropeptides developed using a proprietarybioinformatics platform. Each fluoropeptide encapsulates multiple CD4+ and CD8+ T cell epitopes, derived from conservedinternal influenza proteins, which are predicted to bind to multiple HLA-types thereby granting the vaccine broad populationcoverage irrespective of ethnicity. Flunisyn has completed two dose finding studies in young, healthy adult volunteers andrecently a third study in the elderly population (median age of 71 years).From the clinical studies, Flunisyn was demonstrated to be safe and well tolerated across young and old members of thepopulation, inducing a broad cross-reactive anti-viral CMI response to multiple, distinct influenza A viruses (H1N1 to H9N2).These properties offer the unique position for Flunisyn as a truly pan-influenza A vaccine for seasonal and pandemic use.Flunisyn’s ability to induce a robust immune response in the elderly population is of particular importance where conventional,HA-based influenza vaccines have proven to be poorly effective.BiographyCampbell Bunce has a Ph.D. in Immunology awarded by the School of Medicine, University of Manchester, UK. After a post-doctorate at ImperialCollege, London, he joined the biotechnology sector where he has been developing novel immunomodulating therapies and vaccines for 16 years.Campbell joined ITS as R&D Director in 2009 managing the company through the transition from pre-clinical research to clinical development of theplatform Depovaccine technology. Campbell has published a number of papers on T cell immunology and novel immunomodulating technologies.campbell.bunce@its-innovation.comJ Vaccines Vaccin 2013ISSN: 2157-7560, JVV an open access journalVaccines-2013July 29-31, 2013Volume 4 Issue 5Page 43
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