HOSTS

CO-HOSTS

SPONSORS

CONTENTS

2 ACCESS MAP

3 FLOOR PLAN

4 INSTRUCTION FOR SPEAKERS

5 Welcome Letter

6 Acknowledgements

8 Meeting agenda

10 Abstracts 10 Translational Virology 13 Session I: Hepatitis 15 Session II: Special Session 16 Session III: Arbovirus 20 Session IV: Vaccines 21 Session V: Zoonosis 25 Session VI: Retrovirus (HIV, HTLV-1)

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ACCESS MAP

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FLOOR PLAN

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Instruction for SpeakersINSTRUCTION FOR SPEAKERS

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Welcome to the 8th International Global Virus Network (GVN) Meeting. It is our great honor to both host and welcome you to this Meeting. There are no borders for viruses and we continue to face a range of threats of a number of viral diseases at the same time. It is essential and important to prepare for the threats of viral epidemics through international collaboration and cooperation which is consistent with the goals and the mission of GVN.

The 8th International Global Virus Network Meeting will be jointly held with the annual meeting of The Japanese Society for Virology in Sapporo in which more than 1500 Japanese virologists will attend. We believe that this will provide a good opportunity both GVN and JSV members to exchange the most advanced information to combat global viral threats and to establish new collaborations and networks.

The GVN programs will cover a wide range of topics and will include presentations on epidemiology, diagnostics and pathogenesis. We are cofident this will generate valuable discussions and exchanges will allow the GVN to further develop new strategies in the field and to expand its mission.

Hideki Hasegawa, M.D.,Ph.DCenter Director, GVN Center of Excellence, GVN Scientific Leadership Board

Director,Department of Pathology,National Institute of InfectiousDiseases

Robert C. Gallo, M.D.Co-founder & Scientific Director,Global Virus Network (GVN)

Director,Institute of Human Virology at the University of Maryland School of Medicine

Hirofumi Sawa, M.D., Ph.DDeputy Director, Research Center for Zoonosis Control,Hokkaido University

ProfessorDivision of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University

WELCOME LETTER

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ACKNOWLEDGEMENTSHOSTResearch Center for Zoonosis Control, Hokkaido UniversityGlobal Institution for Collaborative Research and Education (GI-CoRE)National Institute of Infectious DiseasesGlobal Virus Network

Co-HostThe Japanese Society for VirologyNeo-virology: the raison d'etre of viruses

Co-PresidentHideki Hasegawa MD.,PhD., Center Director, GVN Center of Excellence, GVN Scientific Leadership Board. Director, Department of Pathology, National Institute of Infectious DiseasesRobert C. Gallo MD., Co-founder & Scientific Director, Global Virus Network (GVN) Director, Institute of Human Virology at the University of Maryland School of MedicineHirofumi Sawa MD., PhD., Deputy Director, Research Center for Zoonosis Control, Hokkaido University. Professor, Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Professor, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University

Scientific Program CommitteeRobert C. Gallo, MD. Institute of Human Virology, USAWilliam Hall, MD., PhD.University College Dublin, IrelandLuc Willems, PhD., University of Liege, BergiumUlrike Protzer, M.D. Institute of Virology, Technical University of Munich, GermanyHirofumi Sawa MD., PhD., Research Center for Zoonosis Control, Hokkaido University, JapanHideki Hasegawa MD.,PhD., National Institute of Infectious Diseases, JapanNatalia Mercer, PhD. Global Virus Network (Conference Coordinator)

GVN Board of DirectorsChair: Timothy Moynahan. The Moynahan Law FirmAndrew Cheng, MD, PhD. Senior VP of Development Operations, Gilead Sciences, Inc. Jeffrey Schragg (Secretary). Tax Partner at BDOMathew L. Evins (Treasurer). Chairman, Evins Communications, Ltd.Raymond Schinazi, PhD, DSc, Frances Winship Walters Professor of Pediatrics and Director, Laboratory of Biochemical Pharmacology, Emory University School of MedicineRobert C. Gallo, MD. GVN Co-Founder and Scientific Director. Director, Institute of Human Virology at the University of Maryland School of Medicine

GVN Scientific Advisory Board Chair: Robert Gallo, MD. Institute of Human Virology, USAAlexey Mazus, MD. Moscow Center for AIDS Prevention, RussiaAnders Vahlne, MD, PhD. Karolinska Institute-Karolinska University Hospital, SweedenArséne Burny, PhD. Gembloux Agro-Biotech, BelgiumDiane Griffin, MD, PhD. Johns Hopkins University, USAFranco Buonaguro, MD. Istituto Nazionale Tumori “Fondazione Pascale” National Cancer Institute, Italy.Erica Ollman Saphire, PhD. The Scripps Research Institute, USAGlenda Gray, MBBCh, FCPAED - President, Medical Research Council of South AfricaHideki Hasegawa, MD, PhD. National Institute of Infectious Diseases. JapanJames LeDuc, PhD. University of Texas Medical BranchGalveston National Labs, USAJanusz Paweska, DVSc South African NHLS, South Africa.John Glass, PhD. J. Craig Venter Institute, USA.Massimo Palmarini, DVM PhD FRSE. Medical Research Council Glasgow, UKMichael Oldstone, M.D. The Scripps Research Institute, USA

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Peter Palese, MD. Mt. Sinai School of Medicine, USAProtzer Ulrike, MD. Institute of Virology TU Munich, GermanyVictor Romanowski, PhD. Universidad Nacional de La Plata, ArgentinaVolker Erfle, DVM, PhD. TU München Institut für Molekulare Virologie, Germany.William Hall, MD, PhD. Centre for Research in Infectious Diseases, University College Dublin, IrelandYi Zeng, MD. China Centers for Disease Control, China

GVN Senior Advisors Amanda Gutkin, UAEMV Pillai, MD, Professor of Oncology, Thomas Jefferson University; Chair of Oncology, Aster MedCityStanley Plotkin, PhD, Emeritus Professor, University of PennsylvaniaVint Cerf, PhD, Vice President and Chief Internet Evangelist, GoogleWilliam Haseltine, PhD, President, ACCESS Health International, Inc.

GVN Central- StaffAlash’le Abimiku, PhD, GVN Coordinator for low and middle income country (LMIC)Dave Wilkins, CFOEdward McSweegan, PhD, Program DirectorFlorence Haseltine, PhD, MD, Senior IT ConsultantJoyce Johnson, Special Advisor on GrantsManhattan Charurat, PhD, Special Advisor on EpidemiologyMarcus Gallo, MS, Research AssociateNatalia Mercer, PhD, Program DirectorNora Grannell, Director of Public RelationsRaymond Schinazi, PhD, DSc, Frances Winship Walters Professor of Pediatrics and Director, Laboratory of Biochemical Pharmacology, Emory University School of Medicine, Special Consultant on Policies and TherapiesRobert R. Redfield, MD, Special Advisor on Bioterrorism and Clinical Virology

AcknowledgementSponsorsSANOFI （サノフィー）SANOFI PASTEUR（サノフィーパスツール）KYOWA HAKKO BIO., LTD. （協和発酵バイオ株式会社）UMN Pharma Inc. （株式会社UMNファーマ）Toukou Yakuhin Kougyou Inc. （東興薬品工業株式会社）FUJIFILM （富士フィルム）BIKEN （阪大微生物病研究会）IKEDA SCIENTIFIC Co., Ltd. （株式会社池田理化）CHIYODA SCIENCE Co., Ltd. （株式会社チヨダサイエンス）LIFE SCIENCE FOUNDATION OF JAPAN （ライフサイエンス振興財団）Japanese Society for Virologist （日本ウイルス学会）Sapporo City （札幌市）

Advertisement CooperationTakeda Pharmaceutical Company Ltd. （武田製薬株式会社）SRL Inc. （株式会社エスアールエル）Japan Vaccine Co., Ltd. （ジャパンワクチン株式会社）Nippi Inc. （株式会社ニッピ）NIPRO CORPORATION （ニプロ株式会社）IWAI CHEMICALS COMPANY （岩井化学薬品株式会社）

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8th International Global Virus Network Meeting

AGENDA

Time Event

Sunday, 23-Oct6:00-8:00 pm Reception: Faculty House Trillium, Hokkaido University, N11, W8, Kita-ku, Sapporo

Monday, 24-OctGVN & JSV Joint Symposium: "Translational Virology". Moderators: Drs. Hirofumi Sawa and Yasushi Kawaguchi.

9:00-9:30 am Robert Gallo, MD, Institute of Human Virology“HIV vaccines: status of the field and approach from the Institute of Human Virology”

9:30-10:00 am Yasushi Kawaguchi, DVM, PhD, The University of Tokyo"Cell factors involved in a unique nuclear-pore-independent nuclear export system for macromolecular complexes in the nucleus: Potential targets for novel anti-herpetic drugs"

10:00-10:30 am Hideki Hasegawa MD, PhD, National Institute of Infectious Diseases"Mucosal vaccine and application of secretory IgA antibody for Influenza virus infection"

10:30-11:00 am Erica Ollman Saphire, PhD, The Scripps Research Institute"Antibodies Against Viral Hemorrhagic Fevers"

11:00-11:30 am Sharon Lewin, FRACP, PhD, FAAHMS, Peter Doherty Institute University of Melbourne“The current status of HIV cure research”

11:30-1:00 pm lunch

GVN Scientific Meeting. Session I: Hepatitis Moderator: Dr. Anders Vahlne

1:00-1:30pm Shyamasundran Kottilil, MD, PhD, Institute of Human Virology"Treatment of chronic Hepatitis C in 2016: Challenges and Opportunities"

1:30-2:00 pm Esteban Domingo, PhD, Centro de Biologia Molecular Severo Ochoa (CBMSO) "Population dynamics and antiviral interventions examined with the cell culture system of hepatitis C virus".

GVN Scientific Meeting. Session II: Special Session Moderator: Dr. Lothar H. Wieler

2:00-2:30 pm Franco Buonaguro, MD, National Cancer Institute "Fondazione Pascale" "Biomarkers of progression in HPV-related cancers"

2:30-3:00 pm Jonathan Gershoni, PhD, Tel Aviv University"Profiling the IgOme - bioinformatic analysis of serum polyclonal antibodies"

3:00-3:30 pm Coffe/tea break

GVN Scientific Meeting. Session III: Arbovirus Moderator: Dr. Ramesh Akkina

3:30-4:00 pm Richard H. Scheuermann, PhD, J. Craig Venter Institute "Decoding viral genomics using the IRD and ViPR resources: Identification of diagnostic peptide regions in Zika and other Flaviviruses"

4:00-4:30 pm Mario Stevenson, PhD, Univeristy of Miami "Research efforts to combat ZIKA: The Miami GVN site"

GVN & JSV Joint Symposium: "Translational Virology: Room 1 (main Hall) on 1 st Floor GVN Scieentific Meeting Session I to Session VI: Room 7 on 1st Floor

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Joint Hosting: Hokkaido University, Research Center for Zoonosis Control and the Global Institution for Collaborative Research and Education (GI-CoRE) Global Station for Zoonosis Control (GSZ) October 23, 24 & 25, 2016. Sapporo, Japan.

Time Event

4:30-5:00 pm Yongzhen Zhang, PhD, National Institute for Communicable Disease Control and Prevention, China CDC "Arthropods play an important role in the evolution and transmission of virus"

5:00-5:30 pm Marc Lecuit, MD, PhD, Institut Pasteur"Clinical, pathophysiological and biological insights in Chikungunya virus infection"

5:30-6:00 pm Scott Weaver MS, PhD, Galveston National Laboratory"Zika Virus Emergence: History, Evolution, Transmission Cycles and Potential Emergence Mechanisms"

7:00- 9:00 pm Gala dinner

Tuesday, 25-OctGVN Closed Session

9:00-11:00 am GVN's programs

GVN Scientific Meeting. Session IV: Vaccines Moderator: Dr. Harry Kleanthous

11:00-11:30 am Peter Palese, PhD, Icahn School of Medicine at Mount Sinai "Towards a Universal Influenza Virus Vaccine"

11:30-1:00 pm lunch & Press conference

GVN Scientific Meeting. Session V: Zoonosis Moderator: Dr. Victor Romanowski

1:00-1:30 pm Hiroshi Kida, DVM, PhD, Hokkaido University "We are prepared for pandemic influenza"

1:30-2:00 pm Massimo Palmarini, DVM, PhD, Medical Research Council"Transient immunosuppression and the pathogenesis of arbovirus infections"

2:00-2:30 pm Ab Osterhaus, DVM, PhD, University of Veterinary Medicine Hannover"Emerging infections in animals and humans"

2:30-3:00 pm Janusz Paweska, DVSc, National Institute for Communicable Diseases of the National Health Laboratory Service"Origin, epidemiology and the respond to the Ebola epidemic in West Africa, 2013-2015"

3:00-3:30 pm coffe/tea break

GVN Scientific Meeting. Session VI: Retrovirus (HIV, HTLV-1) Moderator: Dr. William Hall

3:30-4:00 pm Seishi Ogawa, MD, PhD, Kyoto UniversityHTLV-1 "Integrated molecular analysis of adult T-cell leukemia lymphoma"

4:00-4:30 pm Luc Willems, PhD, GIGA and GxABT of University of Liège (ULg) Liège"How deltaretroviral ribonucleic acids induce cell transformation"

4:30-5:00 pm Egor Serebriakov, MD, Moscow AIDS Prevention and Treatment Center"Safety and antiviral effect of Elpida (VM-1500), a novel NNRTI (+TDF/FTC) in treatment-naïve HIV-1 infected patients"

5:00-5:30 pm Closing Remarks

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ABSTRACTS"Translational Virology"

Moderators: Drs. Sawa and Kawaguchi.

GVN & JSV Joint Symposium

HIV vaccines: status of the field and approach from the Institute ofHuman Virology

Robert C. Gallo, M.D., George Lewis, PhD, Anthony DeVico, PhD

Institute of Human Virology, University of Maryland School of Medicine& Timothy Fouts, PhD, Profectus BiosciencesBaltimore, Maryland USA

Several HIV vaccine trials using four different approaches have basically failed in preventing HIV infection or was associated with greater infection (one case). One exception was the Thai – U.S. Army trial (RV144) which appears to have given some (very modest) protection in the early months after vaccination.

For several years now emphasis has been on induction of Abs to the HIV envelope component, gp120 rather than a primary induction of cellular immunity to prevent infection based on the logic of the need of preventing integration and establishment of permanent infection. For the U.S. this has mainly evolved around two programs: (1) a very detailed analysis of the RV144 results particularly correlates of protection which have mainly highlighted antibodies interacting with VIV2 gp120 epitopes and epitopes induced by gp120 interactions with CD4, referred to as CD4i Abs which target conserved envelope regions needed for gp120 interaction with CCR5. Functional correlations were mainly with Fc effector functions rather than neutralizing Abs [Nab]. (2) The second major approach is one which is geared to inducing broad Nab, which is a reasonable goal but one not being met since these are proving far more difficult than supposed. Moreover, in monkey studies as well as the results with RV144 correlation of protection is rarely with Nab even when they are generated. At IHV we have a candidate immunogen expressed as a chimeric protein of gp120 and CD4 which has shown some efficacy against heterologous challenges in primates, correlating with CD4i Abs that have Fc effector activity. This vaccine has entered Ph1 trials. Like all gp120 Abs correlating with protection, these Abs are not persisting, and attempts to increase persistence has resulted in over activation of T cells which form more targets for HIV. Persistent boosting to maintain the Abs leads to changes in the Ab isotype that can remove their efficacy. This presentation will summarize these problems which need to be overcome.

　 　

Cell factors involved in a unique nuclear-pore-independent nuclearexport system for macromolecular complexes in the nucleus:

Potential targets for novel anti-herpetic drugs

Yasushi Kawaguchi

The Institute of Medical Science, the University of Tokyo

Vesicle-mediated nucleocytoplasmic transport is a unique mechanism for nuclear export of macromolecular complexes, in which a macromolecular complex in the nucleus buds through the inner nuclear membrane to form a vesicle in the perinuclear space (primary envelopment). This vesicle then fuses with the outer nuclear membrane to release the complex into the cytoplasm (de-envelopment). This type of transport is observed in herpesvirus-infected mammalian cells for nuclear export of the viral nucleocapsids, but is not common in other

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types of cells, indicating that herpesviruses may expropriate this mechanism. However, the cellular mechanism for vesicle-mediated nucleocytoplasmic transport remains largely unknown. In this talk, I will discuss host cell proteins involved in this unique nuclear export system that we have recently identified. I will also discuss the possibilities that these host cell proteins are targets for novel anti-herpetic drugs, since this transport system is essential for the life cycle of herpesviruses and is unique in biology.

　 　

Mucosal vaccine and application of secretory IgA antibody forInfluenza virus infection.

Hideki Hasegawa

　　　　　　　　　　　　　　 Department of PathologyNational Institute of Infectious Diseases

　　　　　　　　　　　　　　 Tokyo, Japan

Secretary Ig A antibodies on the mucosal surface play an important role in protection against influenza virus infection. We have shown that secretary polymeric Ig A antibodies induced by intranasal inactivated influenza vaccine have higher neutralizing and cross neutralizing ability against homologous and heterologous influenza viruses compare to monomeric Ig A antibodies in humans (PNAS 112 (25): 7809-14). However for the samples we analyzed were polyclonal antibodies, so a detailed mechanism of neutralizing activity enhancement by multimerization is still unknown. In this study, the method to produce a secretory multimeric Ig A antibodies in vitro was established, and we examined the improvement of neutralizing effects by multimerization using monoclonal I g A antibodies. The method of in vitro production of multimeric Ig A antibodies were established by introducing cDNA constructs of H, L and J chains of Ig A with secretory component (SC) into Expi293F cells. This method allows us to produce large amounts of recombinant monoclonal polymeric Ig A antibody in vitro. The antibody coding cDNA were isolated and cloned from single plasma cell from subject's peripheral blood mononuclear cells who was intranasally vaccinated with inactivated influenza A (H5N1) vaccine with consent. Monomeric and multimeric the Ig A antibody specific for influenza virus were prepared and functional analysis such as ELISA and neutralization test were performed. We also measured the molecular weight of the antibodies by MALTI-TOF MS to predict the structure. In the present study, we established the method for making polymeric monoclonal Ig A antibodies in vitro. Similar to secretory Ig A antibodies in human nasal wash, the produced recombinant Ig A elucidated that polymerization of the antibody enhance the neutralizing activity. Mass spectrometry analysis of the recombinant monoclonal multimeric Ig A antibodies produced by this method revealed that molecular weight is 720 kDa suggesting mainly consist of tetramer form. These tetrameric Ig A antibodies may be applicable for mucosal route antibody drugs for the prevention and treatment of influenza virus infection.

　 　

Antibodies Against Viral Hemorrhagic Fevers

Erica Ollmann Saphire, Ph.D.

　　　　　　　　　 Professor, Immunology & Microbial Science　　　　　　　　　 Co-Director, Center of Excellence, The Global Virus Network

Director, Viral Hemorrhagic Fever Immunotherapeutic Consortium

Recent outbreaks of Ebola and other viral diseases necessitate rapid development of therapeutics. Monoclonal antibodies offer a promising solution, but it is often unclear how to select the most effective antibodies or combinations for optimal therapy: maximally effective cocktails may require rare antibodies from multiple

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laboratories with potential non-classical functions. A newly formed open consortium aims to galvanize and focus efforts against serious human pathogens using multidisciplinary approaches. Integrated analysis of a large array of antibodies provides a rational basis for the selection of optimized therapeutics, and can lead to rapid understanding of the mechanisms underlying protective efficacy. Structural and biochemical analysis of the most potent antibodies among this broad array illuminates their mechanism of action. Here, we describe the results of a field-wide analysis of antibodies against Ebola virus, a particularly potent antibody against Marburg virus, and a novel panel of antibodies against Lassa virus.

　 　

The current status of HIV cure research

Lewin SR1,2

1 Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne and Royal Melbourne Hospital, Australia

2 Department of Infectious Diseases, Melbourne, Australia

Despite the great success of antiretroviral therapy (ART), treatment of HIV-infected individuals is lifelong. The major barriers to a cure include HIV persistence on ART and impaired immunity. HIV persists predominantly as long lived latently infected resting CD4+ T cells that are found in blood and at higher frequency in tissue. In addition, HIV can persist in specific T-cell subsets enriched in certain tissue sites, including T follicular helper cells in lymph node and Th17 (CCR6+) cells in the GI tract. Long lived infected macrophages, specifically microglia in brain or Kupffer cells in liver, may also play a role although this remains controversial. On ART, HIV-specific T-cells express multiple exhaustion markers and these cells are often unable to recognise and kill an infected cells due to multiple immune escape mutations that are archived in long lived latently infected cells. Furthermore, in some tissue sites such as the B-cell follicle in lymph node, there is limited penetration of HIV-specific T-cells. Several approaches are being tested to achieve HIV remission, including reducing latently infected cells through early ART or latency reversal, boosting immune clearance, reducing immune activation and homeostatic proliferation, eliminating tissue reservoirs and gene therapy to make cells resistant to HIV. We and others have recently completed multiple clinical trials of latency reversing agents (LRA) in HIV-infected patients on ART including histone deacetylase inhibitors (HDACi) and high dose disulfiram. Other interventions include activation of protein kinase C (PKC) with bryostatin and ingenols are under evaluation. Studies of HDACi and disulfiram have demonstrated that HIV transcription can be activated in vivo with varying efficiency, but to date there is no evidence that these interventions alone can clear latently infected cells. In addition we have recently shown in vitro that activating transcription with HDACi, but not other LRAs, may lead to profound changes in HIV RNA splicing therefore limiting potency. Other concerns of HDACi include short and long term toxicity, changes in host gene expression and adverse effects on immune function. More potent and specific LRAs are needed and in development for use alone and in combination. Additional interventions to promote cell death may be needed. Targeting BCL2 or inhibitors of anti-apoptotic proteins (IAP) is being evaluated in vitro and immune mediated clearance with bispecific antibodies, broadly neutralising antibodies and T-cell vaccines are in clinical development. However, even if the frequency of latently infected cells is reduced, long term immune control will be required through therapeutic vaccination and or immunomodulation. Immune checkpoint blockers, including antibodies to CTLA-4 and PD-1, that have recently been licensed for the treatment of melanoma are potentially attractive targets to both enhance HIV-specific T-cells and reverse latency. Clinical trials of these agents are now starting in HIV-infected individuals with malignancy.

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ABSTRACTSSession I: Hepatitis Moderator: Dr. Vahlne

TREATMENT OF CHRONIC HEPATITIS C in 2016: Challenges and Opportunities

Shyam Kottilil MD, Ph.D.

Division of Clinical Care and Research, Institute of Human Virology, Baltimore, MD 21201.

HCV is a positive sense single stranded RNA virus (Family: Flaviviridae, Genus: Hepaciviridae) that preferentially infects hepatocytes and lead to persistent chronic infection. Chronic hepatitis C affects approximately 200 million people worldwide and is a major cause of morbidity, liver cancer, liver transplantation and mortality. Chronic hepatitis C is an asymptomatic disease until the late manifestations of cirrhosis sets in. Over the past two decades, significant advances have been made in the management of hepatitis C. The goal of HCV therapy is to achieve a “functional; cure” defined as sustained virologic response (SVR: absence of detectable plasma HCV RNA levels in blood 12 weeks after stopping HCV therapy). Until recently, interferon-alfa based combination therapy was the only treatment available for chronic hepatitis C. Interferon-alfa is associated with significant adverse events, high drop-out rates, longer duration of therapy (48-72 weeks) and only modest response rates (SVR). Recently, all oral directly acting antiviral therapy has been proved to be safe, tolerable and highly effective in achieving SVR without the use of interferon-alfa. This is a major milestone in the management of chronic hepatitis C and has resulted in overwhelming enthusiasm to treat large number of patients worldwide. Recent studies have suggested that most patients infected with HCV are not aware of the infection and only 20% is engaged in care and less than 10% patients are treated. To accomplish global control of the HCV epidemic, mobilization and prioritization of resources need to occur. Awareness among the providers and patients are required to optimize HCV care continuum in order to prevent the spread of this deadly epidemic. Approaches that enable us to screen new patients, demonstrate effective task shifting of care, develop point of care testing strategies and to engage marginalized patients are critical to achieve global elimination of HCV.

　 　

Population dynamics and antiviral interventions examined withthe cell culture system of hepatitis C virus

Esteban Domingo

Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain

RNA virus population complexity and dynamics is one of the factors underlying the emergence of new viral pathogens, and a major challenge for the control of viral disease. With the availability of a cell culture system for hepatitis C virus (HCV), it is now possible to investigate under controlled environmental conditions the consequences of quasispecies dynamics of this important human pathogen, and to identify vulnerability points for antiviral interventions. We have subjected a molecular clone of the virus to 200 serial passages in human hepatoma Huh-7.5 cells (about 700 days of continuous replication). The design involves a new infection each passage thereby precluding confounding effects derived from host cell evolution. Changes in mutant spectrum composition, replicative fitness, and response to antiviral agents have been studied. Comparison of the mutant spectrum of sequential viral populations suggests a dynamics of replacement of viral subpopulations by others. Fitness increased significantly during the first 100 passages but it did not increase further, despite modification

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of the mutant spectrum and consensus sequence. High fitness HCV populations exhibited resistance to several anti-HCV inhibitors, without the presence of specific drug-resistance mutations. Resistance was observed with inhibitors that display different mechanisms of activity, including the high barrier resistance, direct-acting polymerase inhibitor sofosbuvir. The fitness level arrest paralleled a lack of increase of the fitness-associated drug resistance trait. The results have unveiled a continuous dynamics of HCV mutant spectrum variation, and a limitation of fitness increase despite replication in a constant cellular environment. A new, fitness-associated mechanism of antiviral drug resistance has been identified which is independent of specific resistance mutations. This new mechanism may explain some clinical cases of treatment failure, without evidence of mutations that confer resistance to the relevant drugs.

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ABSTRACTSSession II: Special SessionModerator: Dr. Lothar H. Wieler

Biomarkers of progression in HPV-related cancers

F.M. Buonaguro, M.L. Tornesello and L. Buonaguro

Molecular Biology and Viral Oncology Division & AIDS Refer. Center,　　　　　　　　　Ist. Naz. Tumori "Fond. G. Pascale", Naples – Italy.

Persistent infections of high-risk human papilloma viruses (HR-HPVs) are often associated with progression to mucosal cancers in ano-genital as well as oropharyngeal areas. Also for cervical cancers, for which screening programs are available, it is difficult to identify the lesions at high risk of progression to invasive cancers. Considering that only 1 in 500 HPV-16 positive cervical dysplasias will eventually progress further biomarkers are needed. Tumor progression is characterized by (1) increased expression of viral E6 gene and E6-dependent degradation of p53, and increased expression of E7, known to bind and inactivate pRb; (2) integration of viral DNA into host genome with the consequent disruption of E2 viral gene. Molecular markers able to identify viral infections associated with progressing cervical neoplasia are strongly needed for cervical cancer screening and triage. In particular predictive biomarkers are needed for detecting lesions at high risk of recurrence/progression in order to implement appropriate treatment and for avoiding overtreatment of the those at high probability of regression. In order to achieve such goal we have performed the expression profile analysis of p53-related genes in HPV16-positive genital carcinomas along with autologous non-tumor tissue, and identified significant differences in the expression levels of genes involved in regulation of apoptosis, cell cycle, proliferation and DNA repair pathways. In particular, BRCA1, CDKN2A (p16), CASP2 and TNFRSF10B genes were significantly up-regulated (p<0.05) in cancer lesions and appear to be good candidates for predictive biomarkers. More recently analysis of TERT-gene promoter are showing the high frequency of activating mutations (30.4% of penile cancers as well as 26.1% of cervical cancer) in lesions associated with less oncogenic HPV genotypes (i.e. HPV53), and even in HPV-negative lesions. Validation of these candidate biomarkers is currently in progress on a larger number of cases, including different grades of HPV-related neoplastic lesion (CIN1-3 and invasive cervical cancer). Such studies will contribute to the development of new tools for the identification of premalignant lesions at high risk of progression to invasive cervical carcinoma.

　 　

Profiling the IgOme - the repertoire of antibodies in polyclonal serum.

Jonathan M. Gershoni

Dept. of Cell Research & Immunology, Tel Aviv University

Polyclonal serum consists of vast collections of antibodies. The spectrum of antibody specificities is dynamic and varies with age, physiology, and exposure to pathological insults. The complete repertoire of antibody specificities in blood, the IgOme, is therefore an extraordinarily rich source of information – a molecular record of previous encounters as well as a status report of current immune activity. The ability to profile antibody specificities of polyclonal serum at exceptionally high resolution has been an important and serious challenge which can now be met. Here we describe "Deep Panning" a methodology that merges the flexibility of combinatorial phage display peptide libraries with the power of Next Generation Sequencing to enable high resolution / high-throughput interrogation of the IgOme.

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ABSTRACTSSession III: ArbovirusModerator: Dr. Akkina

Decoding viral genomics using the IRD and ViPR resources:Identification of diagnostic peptide regions in Zika and other Flaviviruses

Alexandra Lee, Brett Pickett, Brian Aevermann, Doug Greer, Brian Reardon,Lucy Stewart, Yun Zhang, and Richard H. Scheuermann

Department of Informatics, J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037, USA

The Influenza Research Database (IRD, www.fludb.org) and Virus Pathogen Resource (ViPR, www.viprbrc.org) are public database and analysis resources supported by the U.S. National Institute of Allergy and Infectious Diseases. IRD focuses on human and animal influenza viruses, while ViPR focuses on human pathogenic viruses in 14 different families, including Coronaviridae, Flaviviridae, Picornaviridae, Togaviridae, Filoviridae and Herpesviridae. Both resources combine three major components – i) an integrated database of genome and protein sequences with enriched annotations, protein structures, immune epitopes, and host response transcriptomics, proteomics, and metabolomics data; ii) a suite of analysis and visualization tools for comparative genomics and host pathway enrichment studies; iii) a workbench function for users to configure their own personal workspaces. As an example of the usefulness of these resources for comparative genomics analysis, we present our work to identify sensitive and specific peptide regions within Zika and other Flavivirus proteins for use in the detection of serum antibodies specific for each of the different Flavivirus species.

Zika virus (ZIKV) is a member of the Flaviviridae family of positive strand ssRNA viruses, which also includes Dengue (DENV), West Nile (WNV), Yellow fever (YFV), Japanese encephalitis (JEV) and St. Louis encephalitis (SLEV) viruses. The ~10.8 kb RNA genome encodes a single polyprotein, which is co- and post-translationally cleaved by proteases into 11 mature peptides. Until 2015, ZIKV had only been detected in sporadic outbreaks in Africa, Asia and the Pacific Islands. In early 2015, ZIKV was detected in eastern Brazil and has rapidly spread throughout the Americas since. While most ZIKV infections are asymptomatic or associated with mild disease, a possible link to neurological syndromes, including Guillain-Barre, has been proposed and a direct link to microcephaly has been established.

It is critical to accurately quantify the incidence and prevalence of ZIKV in affected countries to appropriately prevent, contain, and treat ZIKV infection. However, the ability to diagnose ZIKV infection is complicated by the fact that closely related Flaviviruses, like DENV, YFV, and SLEV, are endemic in the same geographic areas currently experiencing ZIKV outbreaks. Sequence similarity between these viruses makes it difficult to design diagnostic reagents that can detect ZIKV virus or anti-ZIKV serum antibodies with high sensitivity and specificity.

Using mature protein sequence data and comparative genomics tools for multiple sequence alignment and statistical analysis in ViPR, we identified 76 and 82 diagnostic amino acid sites in the ZIKV NS1 and E proteins, respectively, that distinguish ZIKV from all other Flaviviruses with high sensitivity and specificity (>98%). Similar numbers of such diagnostics sites were identified for the other Flavivirus species. Sliding window analysis revealed several contiguous peptide regions that contain multiple diagnostic sites and would be predicted to serve as peptide reagents for detection of serum antibodies specific for each of the different Flaviviruses. Information about immune epitopes and protein solvent exposure is being used to further refine the candidate peptide list for peptide array-based studies. These peptides could be used to measure seroprevalence, detect asymptomatic outbreaks, optimize vaccines, and develop accurate acute and convalescent serum-based diagnostics.

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Research efforts to combat ZIKA: The Miami GVN site

Mario Stevenson PhD.

Department of Medicine, University of Miami Leonard M. Miller School of Medicine, FL, USA

Zika Virus was discovered in 1947 in the Zika Forest of Uganda. Zika Infection of pregnant women can cause devastating effects to the fetus. The virus infects the developing nervous system in the fetus and causes microcephaly in which the infant’s head is significantly smaller than normal. Recent reports indicate that 13% of fetuses in which infection by Zika Virus occurred in the first trimester, will exhibit severe brain defects. As such, there is an urgent need for simple and rapid diagnostics that can identify Zika Virus infected individuals as well as antibodies and a vaccine that can prevent infection by the Zika virus and that can protect the fetus from Zika Virus infection during pregnancy. Miami now lies at the epicenter of Zika in the US. All 19 locally acquired infections, as of August 25th, have occurred in Miami. Therefore, there is a need for a local response to the threat of Zika. Research efforts at the University of Miami Medical School are focused on the development of vaccines and antibodies that can confer protection to Zika Virus infection (Drs. Watkins, Barber and Desrosiers) and to the development of diagnostics that can be used to guide reproductive health for pregnant women and for couples planning pregnancy (Drs. Stevenson and Daunert) Zika research efforts at the University of Miami GVN site will be presented.

　 　

Arthropods play an important role in the evolution and transmission of virus

Yong-Zhen Zhang, Mang Shi, Xin-Cheng Qin, Ci-Xiu Li, Jianguo Xu, Edward C Holmes.

State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Zoonoses, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, 100206, Beijing, China.

Arthropoda is the largest phylum of the animal kingdom with 1,170,000 and 5 to 10 million species, representing over 80% of all known living animal species. They can be found almost all ecological niches. Some of them are well known to harbor and transmit a broad range of pathogens including viruses, bacteria, rickettsiales, and protozoans for humans and animals. However, despite the vast majority in the animal kingdom, little is known about the nature of the ‘virosphere’ in arthropods. Over the past five years, the identification of viruses in arthropods has increased especially rapidly. In this context, we described newly discovered RNA viruses in arthropods collected from China and their evolutionary relationships with well known viruses.

Jingmen tick virus (JMTV) was identified and isolated from Rhipicephalus microplus ticks sampled from China. Its genome comprises four segments, two of which show the evolutionary relationship with the nonstructural protein genes of flaviviruses, while the other two have no sequence homologs. JMTV reveals an unexpected connection between segmented and unsegmented RNA viruses, and provides new clues about the origins of segmented RNA viruses. Additionally, JMTV could infect cattle, but more efforts are need to determine whether they have medical significance. Further investigations revealed the novel and diverse JMTV-like viruses (Jingmen viruses) and flaviviruses in arthropods sampled from China.

More novel negative RNA viruses were discovered in 70 arthropod species including mosquitoes, flies, cockroaches, water striders, ticks, spiders, shrimps, crabs and millipedes sampled from China. In the phylogenetic trees based on the RNA polymerase genes, the newly discovered viruses were spread across the major clades of the negative-sense RNA viruses including arenaviruses, bunyaviruses, orthomyxoviruses, and mononegaviruses. Notably, most of them were basal to these known virus groups.

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Importantly, a completely new virus family (the Chuviridae) was discovered. Interestingly, the Chuviruses exhibited various genome organizations, ranging from non-segmented to bi-segmented and circular genomes. In the phylogenetic trees, the Chuviruses fell between segmented and non-segmented viruses. Therefore, the Chuviruses appears to provide an evolutionary link between segmented and non-segmented negative RNA viruses.

In sum, our data show the remarkable diversity of viruses in arthropods. Our data also suggest that arthropod have played a central role in the evolution and transmission of RNA viruses that cause disease in vertebrates and plants.

　 　

Clinical, pathophysiological and biological insights in Chikungunya virus infection

Marc Lecuit

Biology of Infection Unit, Institut Pasteur, Paris, France

Chikungunya virus (CHIKV) is an arbovirus, for which almost nothing was known a decade ago, when it triggered a massive outbreak in the islands of the Indian Ocean, and disseminated throughout Asia. It has now reached Europe and the Americas. In order to better understand the pathophysiology of this poorly characterized alphavirus, we developed a mouse model of infection. This allowed establishing that CHIKV specifically targets fibroblasts of skeletal muscles, joint capsules, and dermis, and may also disseminate to the central nervous system, where it infects choroid plexuses and the meningeal and ependymal envelopes. These experimental results were confronted to human epidemiological and histopathology data, and this confirmed their significance. We also demonstrated that CHIKV can be vertically transmitted to neonates born from viremic mothers. We also investigated innate immune responses to CHIKV, and shown that type 1 IFN sensing by non-hematopoietic cells is critical for the control of the infection. Following a translational approach, we developed a preventive and curative strategy based on the use of human anti-CHIKV neutralizing antibodies. We also investigated the host factors implicated in the replication of CHIKV and its control. We used a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyzed the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

　 　

Zika Virus Emergence: History, Evolution, Transmission Cyclesand Potential Emergence Mechanisms

Scott C. Weaver

Institute for Human Infections and Immunity and Department of Microbiology & Immunology,　　　 University of Texas Medical Branch, Galveston, USA

Zika virus (ZIKV), a mosquito-borne flavivirus closely related to dengue, yellow fever, West Nile and Japanese encephalitis viruses, was discovered in 1947 during yellow fever surveillance in the Zika Forest of Uganda. The virus was first isolated from a sentinel rhesus macaque and soon thereafter from arboreal Aedes africanus

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mosquitoes collected in the canopy. Further study of enzootic transmission in Africa suggested that nonhuman primates are the major amplifying hosts and that several different arboreal mosquitoes in the genus Aedes can serve as vectors. Although only 14 human infections were documented before 2007, human serosurveys in African and Asia suggested widespread exposure. Following 60 years of relative obscurity, ZIKV emerged in Yap, a small Micronesian Island, to cause just over 100 confirmed and suspected cases of febrile illness accompanied by rash and arthralgia, and epidemiologic studies suggested that up to 73% of the human population was infected. A few years, larger outbreaks began in French Polynesia and other islands in the South Pacific, with an estimated tens-of-thousands of infections and an association of some with Guillain–Barré syndrome (GBS), whose incidence increased 20-fold coincident with the ZIKV outbreak. Then, probably in late 2013, ZIKAV reached Brazil, resulting in 2015 in an explosive outbreak involving over one million estimated cases, presumably transmitted by the peridomestic mosquito A. aegypti and possibly also the invasive species A. albopictus. Sexual transmission has also been detected in travelers returning to non-endemic regions. In the Americas, Zika virus Infections were again associated with GBS but also with over 1,400 confirmed cases of fetal microcephaly coincident in time and space with ZIKV circulation. Subsequently, the virus has spread to the majority of countries in Latin America and the Caribbean, and microcephaly has also appeared in several of these. Here, I will review potential explanations for the sudden and unexpected emergence of ZIKV, and epidemiologic and basic research needed to test these hypotheses to understand these the dramatic spread, predict future trends, and develop control measures as well as products to protect against severe outcomes of infection.

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ABSTRACTSSession IV: Vaccines Moderator: Dr. Kleanthous

Towards a Universal Influenza Virus Vaccine

Peter Palese, Ph.D.

Icahn School of Medicine at Mount Sinai

Despite FDA-approved vaccines and antivirals, seasonal and pandemic influenza remains a serious threat associated with substantial morbidity and mortality. While annual seasonal influenza virus vaccination is effective – albeit underutilized in most countries – a safe universal influenza virus vaccine providing broad and long-lasting immunity would represent a major breakthrough. We have developed vaccine constructs which express chimeric hemagglutinins resulting in the redirection of the immune response away from the immunodominant (variant) head domain of the hemagglutinin toward the much more conserved stalk of the hemagglutinin and the highly conserved neuraminidase. Such vaccine constructs work well in animal challenge models and await extensive clinical trials in humans.

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ABSTRACTSSession V: ZoonosisModerator: Dr. Romanowski

We are prepared for pandemic influenza

Hiroshi Kida, DVM, PhD

Member of the Japan Academy, University Professor of Hokkaido University Specially Invited Professor and Head of the Research Center for Zoonosis Control Sapporo, Japan

It is now believed that each of the past 4 pandemic influenza viruses are the reassortants between the preceding human seasonal influenza virus and avian influenza virus strains. Each of the HA genes of those was originated from a duck influenza virus that is antigenically and genetically highly static. We have shown that pigs are susceptible to each of avian and mammalian influenza viruses, generating reassortants that acquire human receptor specificity. Since each of the subtypes of influenza A virus perpetuates among migratory ducks and their nesting lake water in nature and avian viruses of any subtype can contribute genes in the generation of reassortants in pigs, none of the 16 HA and 9 NA subtypes can be ruled out as potential candidates for future pandemic strains.

We have established a library of 2,400 avian influenza virus strains isolated from ducks with 144 combinations of 16 HA and 9 NA subtypes (https://virusdb.czc.hokudai.ac.jp). Test vaccines prepared from H1N1, H5N1, H6N2, H7N7, H7N9 and H9N2 viruses in the library conferred sufficient immune response to protect chickens, mice, and macaques from the challenge with isolates from poultry birds and humans. Thus we now have vaccine strains for pandemic influenza.

In addition, we strongly propose that drastic improvement of seasonal influenza vaccine is of crucial importance in order to assure the effective preparedness for pandemic influenza. Because current split vaccines prepared by ether- or detergent-disruption are not sufficiently immunogenic, especially in children and the elderly, seasonal influenza vaccines need to be significantly improved. Furthermore, the method for controlling pandemic influenza should be based on measures that are used for the control of seasonal influenza. We believe that inactivated whole virus-based vaccine candidates will provide solutions to the limitations of current influenza vaccines.

In order to accomplish the goal for a new and effective influenza vaccine, the All Japan Collaborating Study Group for the development of influenza vaccine of global standard was established on 8 April 2015. Each of 5 influenza vaccine producers in Japan participates in the program. The goals of the program are;

1) to compare the immunogenicity and safety of whole virus particle vaccine and split vaccines.2) to use the results of these pre-clinical and clinical trials to revise the standard of influenza vaccines for

human use. 3) for each member of the All Japan Group to determine the optimum route of inoculation and to evaluate

any proprietary adjuvant.

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Transient immunosuppression and the pathogenesis of arbovirus infections

Massimo Palmarini

MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom

Arboviruses cause acute diseases and are a major burden to global human and animal health. Studies on the early events of infection are critical in order to understand the pathogenesis of the disease. These studies are difficult to do in humans as they would need to be carried out before the onset of clinical signs. Mouse models are therefore widely used for this scope although they often fail to represent the intricate interplay between host and pathogen, which is shaped by co-evolutionary adaptations. Arboviruses infect in nature a variety of animal species, including livestock.

We study bluetongue, one of the major infectious disease of ruminants. The disease is caused by a midge-transmitted dsRNA virus known as bluetongue virus (BTV). Studies on bluetongue in sheep can offer unique perspectives in understanding arbovirus pathogenesis as observations made in the naturally occurring disease can be effectively reproduced in a convenient experimental setting using the same target animal species (Caporale et al., 2014). The clinical outcome of BTV infection in sheep is extremely variable but, similarly to other arbovirus infections, a rapid onset of the antibody response correlates with a more favourable clinical outcome.

Using BTV, with its natural sheep host, we revealed a previously uncharacterized mechanism adopted by an arbovirus to manipulate host immunity at the early stages of infection. BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes (LN) of the infected sheep. Here, BTV infects and disrupts follicular dendritic cells (FDC). These are cells of stromal origin and promote the formation and maintenance of the germinal centres in which B cells differentiate into memory cells and plasma cells. FDC are also responsible for supporting antibody class switching and affinity maturation.

We show that BTV hinders B cell division in germinal centers, resulting in a delayed production of high affinity and virus neutralizing antibodies. Importantly, the humoral immune response to a second antigen is also hampered in BTV-infected sheep.

Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical, early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease.

　 　

Emerging infections in animals and humans

Ab Osterhaus

‘RIZ’, Hannover, Germany. albert.osterhaus@tiho-hannover.de ‘Artemis One Health’ Utrecht, The Netherlands

Complex relationships between human and animal species have resulted in human-animal interfaces that have promoted cross-species transmission, emergence and eventual evolution of a plethora of human pathogens. Remarkably, most of the characteristics of these interfaces have been established long before the end of our species pre-historical development, to be relentlessly shaped throughout the history of our own and animal species. More recently, changes affecting the modern human population worldwide and their dramatic impact on the global environment have taken domestication, agriculture, urbanization, industrialization, and colonization to unprecedented levels. This has created new global multi-faceted human-animal interfaces, associated with major epidemiological transitions, accompanied by an unexpected rise of emerging and re-

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emerging infectious diseases in humans, that all have their origin in animal reservoirs. Until the beginning of the last century, infectious diseases were the major cause of mortality of humans. Around 1900 infectious diseases caused about fifty percent of human deaths in the western world. In the following decades, this percentage decreased to less than a few percent. This was largely due to the implementation of public health measures such as sewage installment and development of clean drinking water systems, but also to development of vaccines and antimicrobials. Major successes in this regard were the eradication of smallpox and rinderpest through well-orchestrated vaccination campaigns in humans and cattle, respectively. Such successes prompted policymakers and scientists to predict that infectious diseases of humankind and of their domestic animals would eventually be brought under control in the industrialized world. Paradoxically the following decades confronted the world with an ever-increasing number of emerging or re-emerging infectious diseases, some causing true human or animal pandemics. Pathogens spilling over from wildlife reservoirs, either directly or via intermediate hosts, were at the basis of most of these disease outbreaks. Striking examples in humans were the emergence of AIDS from chimpanzees, avian flu from migratory birds, and SARS, MERS, and Ebola from bat reservoirs. A complex mix of predisposing factors in our globalizing world, linked to major changes in our societal environment and global ecology, collectively created opportunities for viruses and other pathogens to infect and adapt to new animal and/or human hosts. This paved the way for the unprecedented spread of infections in humans and animals with dramatic consequences for public and animal health, animal welfare, food supply, economies, and biodiversity. It is important to realize that due to the complex and largely interactive nature of the predisposing factors, it is virtually impossible to predict what the next pathogen threat will be, from where it will come and when it will strike. However better understanding of the underlying processes may eventually lead to predictions that would improve our preparedness for outbreaks in humans and animals. Importantly, the increased emergence of viral infections is largely paralleled by medical, veterinary, technological, and scientific progress, continuously spurred by our never-ending combat against pathogens. Investment in better understanding the human-animal interfaces will therefore offer a future head start in the never-ending battle against infectious diseases of humans.

　 　

Origin, epidemiology and the respond to the Ebola epidemic in West Africa,2013-2015

Janusz T. Paweska

Center for Emerging and Zoonotic Diseases, National Institute for Communicable Diseases (NICD-NHLS), Sandringham-Johannesburg, South Africa

The 2013-2015 Ebola virus disease (EVD) outbreak began in Gueckedou district, Forest Region of Guinea on 26 December 2013, but it was not recognised for several months. From the original epicentre in south-east Guinea the epidemic spread to neighbouring countries and became the largest ever EVD outbreak since its first occurrence in 1976 in Central equatorial Africa.

Ineffective outbreak response in countries previously devastated by civil war, with inadequate healthcare system, under-resourced health facilities, unsafe burial practices, and poor infection control, further fuelled the epidemic. When the epidemic reached health and humanitarian disaster, eventually on 08 August 2014 WHO declared the EVD outbreak in West Africa as Public Health Emergency of International Concern (PHEIC), and on 19 Sept. 2014 the UN Security Council recognised it as Threat to Peace and Security. Massive deployment of resources and international donations began to flow to advert EVD disaster. Thousands of health care and relief workers from countries around the world descended on the towns and cities of Guinea, Liberia and Sierra Leone in a struggle of more than two years to contain the EVD epidemic. The many failures in the Ebola responses and lesson learned prompt a need for transformation of the existing African health systems, including the need for empowerment of the WHO.

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The outbreak of EVD in West Africa has highlighted the need for improved rapid diagnostic assays, vaccines and antivirals. Provision of rapid and more widely accessible diagnostic capacity in West African countries was one of the priorities to combat the Ebola crisis.

In response to the PHEIC caused by EVD epidemic, the NICD established Ebola mobile laboratory (EML) diagnostic capacity in Freetown in August 2014. The Western Urban Area of Sierra Leone, where the NICD teams worked, remained a hotspot of EVD outbreak for months, and for weeks the NICD EML was the only Ebola diagnostic capacity to respond to overwhelming and increasing demands for EVD diagnosis. From the beginning of the EML operation in Freetown, NICD teams undertook training of Sierra Leonean staff in operational logistics of the facility, biosafety and diagnostic procedures. This effort culminated in handover of the EML to the Sierra Leonean Ministry of Health and Sanitation on 24 March 2015. Since then the EML is still operational. As of August 2016 the NICD-established EML tested more than 11 000 clinical specimens from suspected EVD cases. The EML became a valuable site for training of SA staff in diagnosis of dangerous pathogens - life experience for many, and represents the largest Ebola international response in the history of the institute and the country.

Significant progress was made to evaluate Ebola vaccines in the past two years, with promising results for recombinant vaccines. The Global Alliance for Vaccines and Immunization has agreed to stockpile 300 000 doses of pre-licensed Merck’s candidate vaccine (rVSV-ZEBOV), but more data is needed on its safety and efficacy, and the regulatory process in African countries need to be expedited, as well as plans how this vaccine will be used.

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ABSTRACTSSession VI: Retrovirus (HIV, HTLV-1)Moderator: Dr. Billy Hall

Integrated molecular analysis of adult T-cell leukemia lymphoma

Seishi Ogawa, MD, PhD.

Department of Pathology and Tumor Biology, Kyoto University

Adult T-cell leukemia / lymphoma (ATL) is a distinct form of peripheral T-cell lymphoma, which is etiologically associated with human T-lymphotropic virus type I (HTLV-1) infection during early infancy. Although HTLV-1 can effectively immortalize human T-cells, there is a long latency period of ~30-50 years before the onset of ATL, suggesting that HTLV-1 infection alone may be insufficient for the development of ATL, but additional acquired genetic events that occur during the later life are essential for its pathogenesis. To elucidate a complete registry of the genetic events involved in the pathogenesis of ATL, we performed an integrated molecular study comprising whole-genome/exome and RNA sequencing (RNA-seq) combined with array-based methylation and genomic copy number analysis among a cohort of 50 paired ATL samples with extensive validation using targeted deep sequencing of detected mutations in >300 follow-up samples. In the majority of ATL cases, transcription of the sense-stranded genes, including tax, gag/pol/env, and other integral viral genes, are largely suppressed, whereas antisense transcription, encoding HBZ protein, was maintained. ATL genomes had a large burden of mutations, copy number alterations (CNAs), and other structural variations, by which a number of functional pathways relevant to T-cell functionalities are affected by gene mutations and copy number alterations, including T-cell receptor/NF-κB signaling (PLCG1, PKCB, CARD11, VAV1, RELA, RHOA, and IRF4), G-protein-coupled receptors (CCR4, CCR8, and GPR183) and other signaling (STAT3, ATXN1, NOTCH1, and CSNK2A1), transcriptions (BCL11B, GATA3, IKZF2, and PRDM1), epigenetic regulation (TET2, EP300, and SETD2), and immune surveillance (CD274, CD53, FAS, HLAs, and B2M). In total, 50 genes were significantly mutated, of which 13 genes were mutated in more than 10% of the cases. Conspicuous features of genetic alteration in ATL include very high frequency of involvement of TCR/NF-κB signaling immune surveillance pathways, predominance of gain-of-function alterations and, and a significant enrichment in the tax interactomes. These findings suggest that HTLV-1 infected cells escape immune surveillance by mutations and silencing of their integral components, especially tax, as well as alterations in immune surveillance machineries and at the same time replace the oncogenic tax functions with somatic mutations in tax-interactome genes. Finally, several components of the TCR/NF-κB signaling pathway is thought to be a plausible therapeutic targets to improve the outcome of ATL.

　 　

How deltaretroviral ribonucleic acids induce cell transformation

Luc Willems

GxABT and GIGA, University of Liège, Belgium

Approximately 17% of human cancer cases occurring worldwide are caused by one of 6 human viruses. Among the strategies developed by viruses to escape the host immune response, mechanisms involving viral non-coding RNAs have recently been discovered. Viruses can express microRNAs that directly target cellular transcripts while others produce long non-coding RNAs acting as microRNA sponges or epigenetic modulators. These strategies based on ribonucleic acids control the cell fate without eliciting an immune response due to

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the absence of viral proteins. Evidence on viral non-coding RNAs expressed by two related deltaretroviruses, human T-lymphotropic virus (HTLV-1) and its animal model (BLV) will be presented.

　 　

Safety and antiviral effect of Elpida (VM-1500), a novel NNRTI (+TDF/FTC)in treatment-naïve HIV-1 infected patients

T.E. Shimonova, E.M. Serebriakov, E.A. Orlova-Morozova, F.I. Nagimova, O.A. Kozirev, A.V. Kravchenko

Speaker: E.M. SerebriakovHead of the Organizational and methodical department of the Moscow AIDS center.

Objective: to evaluate safety and antiviral efficacy for different treatment regimens with VM-1500/TDF/FTC in comparison with EFV/TDF/FTC in treatment-naïve HIV-1 infected patients.

Methodology: A randomized, placebo-controlled, double-blind dose-finding study in patients with HIV infection who are antiretroviral therapy-naïve with HIV-1 RNA 4.6-4.9 log10 copies/ml and CD4-lymphocytes - 311-379 cells/mm3. Study Stage 1 included 90 HIV-1-infected patients who had not previously received ART. Patients were randomized into 3 groups: 1) VM-1500 20 mg daily; 2) VM-1500 40 mg daily; 3) EFV 600 mg daily. All patients received TDF/FTC also. In treatment-naïve patients, VM-1500 20 and 40 mg QD (with TDF/FTC) at week 12 demonstrated potent antiviral activity, comparable to EFV, and favourable safety/tolerability profile. Fewer drug-related AEs were observed for VM-1500 compared with EFV. VM-1500 20 mg QD was selected for further study.

Study Stage 2 included 150 HIV-infected patients, separated in two groups. 1) VM-1500 20 mg daily (30 patients previously received VM-1500 20mg on Stage 1, 30 patients switched from VM-1500 40 mg after Stage 1, 30 new patients); 2) EFV 600 mg daily (30 patients previously received EFV on Stage 1, 30 new patients). All of the patients continue to receive TDF/FTC. An interim analysis of virological efficacy for patients who received 20 mg daily (with TDF/FTC was performed after 12 weeks (Study Stage 2) of treatment.

Results: The 24, 36, 48-week ART regimen including VM-1500 at dose of 20 mg in combination with TDF/FTC showed the same efficacy as the EFV + TDF/FTC regimen regardless of the baseline level of HIV RNA. The proportion of patients with a HIV RNA level of < 50 copies/ml was highest in VM-1500 20 mg group and amounted to 93.3% after 24, 36 and 48 weeks of treatment, while in EFV 600 mg group this level was 76.9%, 88,5% and 84,6% respectively.

In Group 1 VM-1500 20 mg the incidence of Grade 3-4 adverse events (AEs) was minimal (8,3%) in comparison with patients from Group 2 EFV 600mg (15.5%). AEs of special interest (impairments of the central nervous system and mental activity) were substantially rarer in Group 1 VM-1500 20mg (23.3%) than in Group 2 EFV 600mg (60.3%). There were no skin AEs in Group 1 VM-1500 20mg while in Group 2 EFV 600mg there were 17.2%.

Conclusions: In treatment-naïve patients, VM-1500 20 QD (with TDF/FTC) at week 24-48 demonstrated potent antiviral activity, comparable to EFV, and favourable safety/tolerability profile. Fewer drug-related AEs were observed for VM-1500 Elpida compared with EFV.

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BIOS

Ramesh Akkina is a professor of Microbiology, Immunology, and Pathology at Colorado State University, Fort Collins, USA. A PhD from the University of Minnesota, Minneapolis, he also served as a visiting professor at the UCLA School of Medicine, Los Angeles. His early contributions were in Influenza virology and stem-cell based gene therapy strategies. His lab pioneered in work with humanized mice for HIV and Dengue research and recently developed new pre-exposure prophylaxis methods to prevent HIV transmission, successfully tested anti-HIV si-RNAs and aptamers and showed that immune exhaustion during HIV infection can be partly reversed by PD-1 blockade.

Present work is centered on HIV latency, prevention, novel therapeutics and evolution. His research is supported by multiple NIH grants. He is a member of many editorial and international grant review boards, and currently serves as a Center Director for Global Virus Network branch at Colorado State University.

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Franco Buonaguro is currently the Director of Molecular Biology and Viral Oncology Unit, in the Department of Experimental Oncology at the Istituto Nazionale Tumori “Fondazione Pascale”, Naples - Italy. Dr Buonaguro has worked on various aspects of cancer pathogenesis including chemical, physical and viral carcinogenesis. His current research area is mainly focused on pathogen-associated cancers, including HPV and genital cancers, HHV-8 and Kaposi’s sarcoma, HBV/HCV and liver cancer. Dr Buonaguro gained his MD doctoral degree (1977) from Federico II University in Naples, board certified in Endocrinology (1982) as well as in Microbiology and Virology (1992), he has

subsequently worked in Chicago, at the Argonne National Laboratory, and in Seattle, at the Fred Hutchinson Cancer Research Center. He was a recipient of WHO Fellowship in 1983; and has served as WHO Virology Consultant of WHO/ UNAIDS Network for HIV Isolation and Characterization (since 1996) and WHO HPV DNA International Collaborative Study Group (2003). He is author/co-author of > 150 PubMed indexed articles, with H-index of 33 and i10-Index of 91. In 2010 he contributed to the IARC Monograph 100 (vol B) on the Evaluation of Carcinogenic Risks to Humans by Biological Agents. He established and is the Editor in chief of Infectious Agents and Cancer the online journal published since 2006 by BioMed Central with the IF (2014) of 2,36. He is also currently Director of the East Africa AIDS Research Center in Uganda, established in 1996 by the World Laboratory, Geneva.

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Esteban Domingo received a B.Sc. in Chemistry from the University of Barcelona (1965) and a Ph.D. in Biochemistry (1969). He did postdoctoral work at the University of California, Irvine, and University of Zürich, working with Dr. Charles Weissmann (1974- 1977). This work permitted the first calculation of a mutation rate for an RNA virus, and the first evidence of quasi-species in an RNA virus. His main interests are the biological implications of high mutation rates and quasi-species dynamics of RNA viruses, and to develop new antiviral strategies. He is presently Emeritus Professor of the Spanish Research Council (CSIC) at Centro de Biología Molecular Severo Ochoa in Madrid. He has

published over 360 research papers and several books and book chapters. He is a member of EMBO, the European Academy, and the Royal Academy of Science of Spain, and has been awarded honorary degrees by the Universities of Liège and Bern.

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Robert Gallo, M.D., Co-founder & Scientific Director of the Global Virus Network (GVN), The Homer & Martha Gudelsky Distinguished Professor in MedicineDirector, Institute of Human Virology at the University of Maryland School of Medicine.Dr. Robert Gallo is Co-Founder and Scientific Director of the Global Virus Network, formed in 2011. He is also Director of the Institute of Human Virology (IHV) at the University of Maryland School of Medicine (a GVN Center of Excellence) and previously spent 30 years at the National Cancer Institute, as head of Tumor Cell Biology. Dr. Gallo is renowned for his research on HIV, most notably his co-discovery in 1984 that HIV

(a retrovirus) was the cause of AIDS and his development of the HIV blood test. Previously, Dr. Gallo and his colleagues discovered the first human retrovirus, HTLV-1, a cause of adult T cell leukaemia. The discoveries of all human retroviruses (HTLV and HIV) were dependent on Dr. Gallo and his co-workers earlier discovery in 1976 of interleukin-2 (IL-2), a growth factor for human T cells, which enabled scientists to culture human T cells for virus isolations. IL-2 is now also used widely in cancer treatments. In 1986, he and his co-workers isolated human herpes virus 6 (HHV-6), the first new human herpes virus discovered in more than 25 years. Later, others showed HHV-6 caused Roseolla. In 1996, with his co-workers, they discovered that some natural compounds known as chemokines can block HIV was hailed by Science magazine as that year’s most important scientific breakthroughs. Dr. Gallo’s current research at the IHV combines the disciplines of research, patient care, and prevention programs in a concerted effort to speed the pace of medical breakthroughs. He is a principal investigator for a HIV vaccine candidate that entered human trials last fall and continues to research viruses that cause cancer. Dr. Gallo has authored over 1,200 scientific publications as well as the book "Virus Hunting - AIDS, Cancer & the Human Retrovirus." Along with several other international major awards, he has been awarded 34 honorary doctorates and was twice recipient of the Albert Lasker Award in Medicine (1982 and 1986). He is a member of the National Academy of Sciences and the Institute of Medicine and was the most cited scientist in the world 1980-1995.

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Jonathan M. Gershoni completed his BSc in Biology and PhD in Biochemistry at the Hebrew University of Jerusalem. He then did Post-doctoral training with Prof. George E. Palade at Yale School of Medicine where he began his research on the interplay of viruses and their targets and the defense mechanisms of the immune system. Returning to Israel in 1983 he joined the Department of Biophysics at the Weizmann Institute of Science where he continued his study of the molecular events that govern viral infection. He subsequently joined the Laboratory of Tumor Cell Biology at the National Institutes of Health in Bethesda, MD to work with Dr. Robert C. Gallo on developing new approaches

to AIDS therapy and prevention. In 1990 he returned to Israel as one of the founders of the new Department of Cell Research and Immunology at Tel Aviv University where he has served as chairman (2003-2006). Over the last decade Prof. Gershoni has focused on developing new methods for the rational design of vaccines to such pandemic diseases as AIDS, Hepatitis C, influenza and SARS. Prof. Gershoni continues to investigate the humoral response towards viral pathogens; developing computational methods to profile the IgOme - the complete repertoire of antibodies in polyclonal sera, and developing novel approaches for epitope based vaccines and next generation diagnostics.

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William Hall, GVN-Co-Founder, is the Director of the Centre for Research in Infectious Diseases (CRID) and Professor at the Centre for Zoonosis Control, Hokkaido University, Sapporo Japan. Professor Hall’s research interests are primarily on blood-borne viruses which include the human retroviruses, the human T lymphotropic viruses (HTLVs) and human immunodeficiency viruses (HIVs). Professor HaII has also recently established a high profile collaboration and programme, the Ireland Vietnam Virology Initiative with the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi, Vietnam to carry out studies on HIV, Hepatitis B and C and arbovirus infections in that country.

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Hideki Hasegawa graduated from Hokkaido University school of medicine in 1993 with M.D. and finished Ph.D. in 1997. He studied at the Rockefeller University from 1995 to 1996, and University College Dublin from 1996 to 1997. He joined to National Institute of Infectious Diseases (NIID) where he had spent his research of infectious diseases at department of pathology in 1997. In 2003 he promoted to Chief of Laboratory of Infectious Diseases Pathology, at NIID where he is extending his research to development of mucosal vaccine against influenza viruses. In 2011 he promoted to Director of Department of Pathology at NIID.

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Yasushi Kawaguchi is currently vice dean and professor of the institute of medical science, the university of Tokyo (IMSUT). He is also director of research center of Asian infectious diseases and concurrent professor of international research center for infectious diseases in IMSUT. He received his PhD degree from the university of Tokyo and performed postdoctoral training at the University of Chicago with Dr. Bernard Roizman. His work over 25 years has concentrated on the molecular mechanisms of herpesviral replication and pathogenesis.

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Hiroshi Kida, DVM, Ph.D. Member of the Japan Academy, University Professor, Hokkaido University Specially Invited Professor and Head of the Research Center for Zoonosis ControlSapporo, Japan. Member of the Japan Academy; University Professor, Hokkaido University; Specially Invited Professor and Head, Hokkaido University Research Center for Zoonosis Control; Head, OIE World Reference Laboratory for Avian Influenza; Head, WHO Collaborating Centre for Zoonoses ControlPUBLICATIONS: 314 original articles and 148 book chapters and reviews

RESEARCH INTERESTS: Ecology and pathogenesis of influenza viruses, Zoonoses, Vaccinology AWARDS: Japan Academy Prize, The Japan Prize of Agricultural Science, Animal Science Prize, All Japan Agriculture Decoration, The Japanese Society of Veterinary Science Award, and others

Presenting Author Contact Hiroshi Kida Research Center for Zoonosis Control, Hokkaido UniversityKita-20, Nishi-10, Kita-ku, Sapporo, 001-0020, JapanPhone number: +81-11-706-9500Email: kida@vetmed.hokudai.ac.jp

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Shyam Kottilil is the Professor of Medicine and Associate Chief of the Division of Clinical Care and Research at the Institute of Human Virology (University of Maryland). He trained at Brown University and at the National Institutes of Health prior to his appointment at University of Maryland. He is a national leader in the management of hepatitis C infection and has conducted several clinical studies in the inner city community clinics in District of Columbia and Baltimore. He has published over 150 peer reviewed publications and serves as a member of the National HCV Treatment Guidelines Committee.

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Marc Lecuit obtained his MD from the Paris Descartes University Medical School and PhD from the Paris Diderot University and Institut Pasteur. ML is head of the Biology of Infection Unit at Institut Pasteur and Inserm, Professor at Paris Descartes University, and Deputy Head of the Department of Infectious Diseases and Tropical Medicine at the Necker Enfants Malades University Hospital, in Paris-F. ML and his team have developed a mouse model for Chikungunya virus (CHIKV) infection, in which they have identified CHIKV cell and tissue tropisms and studied host responses to CHIKV. They have identified the molecular basis of CHIKV species specificity. They demonstrated that CHIKV can be

transmitted vertically and is neurotropic in neonates, and shown that grafts can transmit CHIKV. They have developed a therapeutic and preventive strategy for Chikungunya. They are currently working on the cell biology of CHIKV infection, to better understand its replication and identify putative therapeutic targets.

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Sharon Lewin, FRACP, Ph.D., FAAHMS. Sharon Lewin is an infectious diseases physician and basic scientist and is the inaugural director of the Peter Doherty Institute for Infection and Immunity; Professor of Medicine at the University of Melbourne; and consultant infectious diseases physician, Alfred Hospital, Melbourne, Australia. The Doherty Institute is a joint venture of the University of Melbourne and Royal Melbourne Hospital and has over 700 staff working entirely on infection and immunity. Her research focuses on the basic biology and clinical trials related to HIV latency and cure, immune reconstitution and HIV-HBV pathogenesis. She has given over 100 major international

invited talks on HIV cure and is regarded as a global leader in HIV cure research. Her laboratory is currently funded by the NHMRC, the National Institutes for Health, The Wellcome Trust, the American Foundation for AIDS Research and multiple commercial partnerships. She was the local co-chair for the International AIDS Conference held in Melbourne in July 2014 which attracted over 14,000 participants and was the largest health conference ever held in Australia. Later that year, she was named Melburnian of the Year. In 2015, she was awarded the Peter Wills Medal by Research Australia and was the first woman to receive this award. She is chair of the Ministerial Advisory Committee for Blood Borne Viruses and Sexually Transmitted Infections, the peak advisory committee to the Minister of Health of Australia. She is a member of the NHMRC Council and chairs the NHMRC Health Translation Advisory Committee and in 2014.

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Seishi Ogawa, MD, Ph.D. Professor at the department of Pathology and Tumor Biology, Kyoto University since 2013. He has been working on genetic analysis of human cancers. His scientific contribution has been central to the understanding of the pathogenesis of myelodysplastic syndromes (MDS), clear cell renal carcinoma, neuroblastoma, and other hematological malignancies, through identification of key genetic alterations and mutations.

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Erica Ollmann Saphire, Ph.D. is a Professor of Immunology and Microbial Science at The Scripps Research Institute. Her research uses structural biology to understand and defeat viral pathogens. Her team has explained how filoviruses drive themselves into cells, how they suppress immune function, where antibodies can defeat them, as well as the structure of the entire human antibody itself. A recent discovery expanded the central dogma of molecular biology by proving that certain viral proteins actually rearrange into different structures at different times for different functions. Her work has been recognized with a PECASE, by the Burroughs Wellcome Fund, by young investigator

awards from ASBMB and ASM, the Lilly–Elanco Research Award which is the oldest and most prestigious award of the ASM, and by the Surhain Sidhu award for the most outstanding contribution to the field of diffraction by a person within five years of the Ph.D. She is a Fellow of AAM and AAAS, serves on the Scientific Leadership Board of the Global Virus Network and is the director of the Viral Hemorrhagic Fever Immunotherapeutic Consortium. This organization, the VIC, united the field into a single force to understand and provide antibody therapeutics against Ebola, Marburg, Lassa and other viruses.

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Ab Osterhaus, DVM, Ph.D. has been Head of the Department of Viroscience at Erasmus MC Rotterdam until July 1st 2014, is currently Professor of Wildlife Virology and Virus Discovery at Utrecht University, and Director of the Center of Infection Medicine and Zoonosis Research and Guest-Professor at the University of Veterinary Medicine Hannover. He has a long track record as a scientific researcher and Principal Investigator of numerous major scientific projects. At Erasmus MC, Professor Osterhaus has run a diagnostic virology lab with more than 40 staff and a research Virology lab with over 150 personnel. His research programme follows a novel integrated “viroscience” concept,

bringing together world-leading scientists in molecular virology, immunology, epidemiology, pathogenesis, and intervention studies on human and animal virus infections. Among the major accomplishments are the discovery of more than 50 viruses of humans and animals (e.g. in humans: influenza A H5N1 virus, human metapneumovirus, human coronaviruses, influenza viruses), elucidation of the pathogenesis of major human and animal virus infections, and development of novel intervention strategies. This has enabled health authorities like the WHO to effectively combat disease outbreaks like SARS and avian influenza. The spin-off, Viroclinics Biosciences BV, is another societally relevant success, allowing effective testing and refining of diagnostic tools and other intervention strategies. The international recognition of Professor Osterhaus is further highlighted by his chairmanships of many international organizations, awards, prizes, guest lecture invitations, (co-)organiserships of international meetings and editorships of scientific journals. Professor Osterhaus has acted as PhD mentor for more than 75 students and holds several key patents. He is also the author of more than 1100 papers in peer-reviewed journals, together cited more than 50,000 times, and his H index is 97. Most of all, Professor Osterhaus firmly believes that scientists have a role to play in translating their knowledge for the benefit and protection of society.

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Peter Palese is Professor of Microbiology and Chair of the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York. His research is in the area of RNA-containing viruses with a special emphasis on influenza viruses. Specifically, he established the first genetic maps for influenza A, B, and C viruses, identified the function of several viral genes, and defined the mechanism of neuraminidase inhibitors (which are now FDA-approved antivirals). He pioneered the field of reverse genetics for negative strand RNA viruses, which allows the introduction of site-specific mutations into the genomes of these viruses. This technique is crucial for the study of the structure and

function relationships of viral genes, for investigation of viral pathogenicity, and for development and manufacturing of novel vaccines. An improvement of the technique has been effectively used by him and his colleagues to reconstruct and study the pathogenicity of the highly virulent, but extinct, 1918 pandemic influenza virus. His recent work in collaboration with García-Sastre has revealed that most negative strand RNA viruses possess proteins with interferon antagonist activity, enabling them to counteract the antiviral response of the infected host. At present, Palese’s group works with Adolfo García-Sastre and Florian Krammer on the development of a universal influenza virus vaccine. He was a recipient of the Robert Koch Prize in 2006, a recipient of the European Virology Award (EVA) in 2010, a recipient of the 2012 Sanofi-Institut Pasteur Award, and the awardee of the 2015 Beijerink Virology Prize of the Royal Netherlands Academy of Arts and Sciences. He is a Member of the National Academy of Sciences (2000), a Corresponding Member of the Austrian Academy of Sciences (2002), a Member of The German Academy of Sciences Leopoldina (2006), a Member of the National Academy of Medicine (2012) and a Fellow of the American Academy of Arts and Sciences (2014).

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Massimo Palmarini is the Director of the MRC-University of Glasgow Centre for Virus Research and Chair of Virology at the University of Glasgow. A veterinarian by training, his research programmes focus on the biology, evolution and pathogenesis of animal arboviruses and on the mechanisms of virus cross-species transmission. Massimo Palmarini’s laboratory is funded by the Wellcome Trust and MRC and his studies have been published in major scientific journals including Science, PNAS, PLoS Pathogens and others. Massimo Palmarini has been elected Fellow of the Academy of Medical Sciences, of the Royal Society of Edinburgh and of the Royal Society of Biology and he was a

Wolfson-Royal Society Research Merit Awardee. He is a member of the Infection and Immunity Board of the Medical Research Council.

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Janusz T. Paweska is a head of the Center for Emerging and Zoonotic Diseases at the National Institute for Communicable Diseases of the National Health Laboratory Service (NICD-NHLS), Sandringham, South Africa. He is also the head of the WHO Collaborating Center for Reference and Research on Viral Haemorrhagic Fevers and Arboviruses, regional director of the Global Virus Network and the deputy director of the Southern Center for Infectious Diseases Surveillance. His special fields lie in viral diagnostics with focus on the development and validation of novel techniques for rapid pathogen detection and discovery, epidemiology and ecology of arboviruses and viral hemorrhagic

fevers, virus-host interactions, management of high and maximum biocontainment facilities. He published 151 articles in peer reviewed journals and 13 book chapters. Prof. Paweska has been a part of international research expeditions and outbreak responses, including the 2002 Ebola outbreaks in Gabon, the 2005 Marburg disease outbreak in Angola, the 2006 Rift Valley fever outbreak in Kenya, the 2009 Ebola outbreak in the Democratic Republic of Congo (DRC), and the Ebola ecology study in 2010, 2011 in the DRC. During a highly fatal nosocomial outbreak in Johannesburg in 2008 he led the discovery of a new Old World Arenavirus, he named Lujo virus. In

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2014 he established Ebola diagnostic mobile laboratory in Sierra Leone as a part of WHO-GOARN Ebola outbreak response in West Africa in 2014-2016. Prof. Paweska is a Lead of South African Global Health Security Agenda in Zoonotic Disease, and a member of a number advisory/expert working groups/committees, including Bioweapon Working Committee of the South African Council for Non-Proliferation, South African Ministry of Health Advisory Committee on Ebola, WHO Global Outbreak & Alert Response Network, WHO Emerging and Dangerous Pathogens Laboratory Network, WHO Technical Group for orthopoxvirus/smallpox virus laboratory diagnostics, WHO Ebola Virus Persistence Study Independent Data Monitoring Committee and the International Committee for Taxonomy of Viruses (ICTV) Filoviridae Study Group.

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Victor Romanowski, Ph.D. is a Professor and Senior Investigator at the Institute of Biotechnology and Molecular Biology at the University of La Plata (UNLP) and the National Research Council (CONICET), Argentina. He earned his PhD degree in Biochemical Sciences from the UNLP and moved to the United States for a posdoctoral training as an Associate Researcher at the Dept. of Microbiology, The University of Alabama at Brimingham (UAB). Several years after returning to Argentina and starting his own research group in Molecular Virology, he spent a few months as a visiting researcher in Oxford, UK. His research interests include fundamental and applied aspects of the

molecular biology of arenaviruses and baculoviruses, as documented in numerous contributions in refereed journals and book chapters. He is a codiscoverer of the ‘ambisense’ coding strategy for ssRNA viral genomes (Arenaviridae), determined the nucleotide sequence for Junín virus, the etiologic agent for Argentine Hemorrhagic Fever (AHF), developed a fast and early specific diagnostic test for AHF, described a new insect virus (EpapGV) specific for a major soyben pest in Argentina and determined its full genome sequence, developed an efficient recombination system for another insect virus (AgMNPV) in order to improve its bioinsecticidal capacity in temperate climats, etc.

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Hirofumi Sawa, M.D., Ph.D. Deputy director of the Research Center for Zoonosis Control, Hokkaido University; Member of the Global Virus Network (GVN). Dr. Hirofumi Sawa is deputy director of the Research Center for Zoonosis Control, Hokkaido University, Japan. Dr. Sawa graduated from the Hokkaido University School of Medicine in 1986 and obtained his Ph.D. in 1990 in the Graduate School of Medicine, Hokkaido University. Dr. Sawa became the Professor of the Division of Molecular Pathobiology in the Research Center for Zoonosis Control, Hokkaido University. The Research Center for Zoonosis Control, Hokkaido University was established in 2005. Dr. Sawa was appointed as the

deputy director of the Center in 2010. Dr. Sawa’s research group has conducted epidemiological viral research in Zambia. The Research Center for Zoonosis Control, Hokkaido University established the Hokudai Center for Zoonosis Control, equipped with BSL-2 and -3 facilities, at the School of Veterinary Medicine, University of Zambia in 2007. There is now a 30 year history of collaborative research between the University of Zambia and Hokkaido University. Dr. Sawa is a visiting professor in the School of Veterinary Medicine, University of Zambia. His group is now extending their epidemiological studies in other geographic regions. His research group also works on the investigation of virus-host interaction mechanisms, the development of diagnostic tools and antiviral therapeutic strategies for arboviral and neurotropic viruses in collaboration with the pharmaceutical company. He has published 216 scientific articles in Nature Medicine, Nature Communication, Science, Proc Natl Acad Sci USA, EMBO Report, and so on.

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Egor Serebriakov is the head of the organizational-methodological department of Moscow center for AIDS prevention and treatment. Dr. Serebriakov’s team in the Moscow AIDS Center is organizing the provision of medical care to HIV-infected patients in Moscow, developing legal documents, participates in the development of the main city activities on different aspects of prevention, diagnostics and treatment of HIV infection. Currently, there is more than 28 000 patients under medical observation in the Moscow AIDS center.

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Richard H. Scheuermann, Ph.D. is the Director of Informatics at the J. Craig Venter Institute (JCVI) and a Professor of Pathology at U.C. San Diego. He received a B.S. in Life Sciences from the Massachusetts Institute of Technology, and a Ph.D. in Molecular Biology from the University of California, Berkeley. After completing his doctoral research, he accepted an independent research position at the Basel Institute for Immunology in Switzerland. In 1992 he joined the faculty in the Department of Pathology at the University of Texas Southwestern Medical Center in Dallas where he rose to the rank of Professor with tenure. In 2001 he made a career shift into the

discipline of bioinformatics, initiated with a sabbatical year at the San Diego Supercomputer Center. In 2012 Dr. Scheuermann moved to San Diego to become the Director of Informatics at JCVI. Dr. Scheuermann has applied his deep knowledge in molecular immunology and infectious disease toward the development of novel computational data mining methods and knowledge representation approaches, including the development of biomedical ontologies and their use in data mining, novel methods for the analysis of gene expression, protein network and flow cytometry data, and novel comparative genomics methods. These computational methods have been made available through several public database and analysis resources, including the Influenza Research Database (IRD; www.fludb.org), the Virus Pathogen Resource (ViPR; www.viprbrc.org) and the Immunology Database and Analysis Portal (ImmPort; https://immport.niaid.nih.gov/) supported by the U.S. National Institutes of Health.

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Mario Stevenson is currently Professor in the Department of Medicine, Chief of the Division of Infectious Diseases, Director of the University of Miami AIDS Institute, Director of the Global Virus Network at the University of Miami and Co-Director of the Center for AIDS Research. Prior to 2011, Dr. Stevenson was the David Freelander Chair for AIDS Research at the University of Massachusetts Medical School and the Director of the Center for AIDS research at that Institution. Dr. Stevenson obtained his BSc. (1980) and PhD (1984) in Glasgow, Scotland. Dr. Stevenson is a molecular virologist who has been working on the viral etiology of AIDS for over 25 years. Dr. Stevenson has published

over 100 peer-reviewed papers and his research has provided fundamental insight into the mechanisms regulating HIV replication and disease pathogenesis. Dr. Stevenson has served as Chair of the HIV AIDS Virology Study Section at the National Institutes of Health, Chair of the Scientific Advisory Board of the National AIDS Conference (CROI), and has served on the NIH Office of AIDS Research that sets AIDS research directives. From 2006-2015, he served as Chair of the Scientific Advisory Board and a member of the Board of Trustees of the American Foundation for AIDS Research (amfAR) and a scientific board member of the Elizabeth Glaser Pediatric AIDS Foundation. Dr. Stevenson has received a Merit Award (10 year grant) from NIH-NIAID. Dr. Stevenson is a recipient of Harvard Medical School’s Shipley Lectureship, recipient of the Gertrude Elion award and Barcelona’s IRSI-Caixa award for accomplishments in AIDS research and is a Fellow of the American Academy of Microbiology. Dr. Stevenson serves on the scientific advisory boards of the Centers for AIDS Research at UC San Diego, Emory University and Case Western Reserve University.

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Anders Vahlne, M.D., Ph.D. is the former head of the Division of Clinical Virology at Karolinska Institutet in Stockholm, the largest Medical University in Sweden. He was also director of the Clinical Virology Laboratory at the Karolinska Hospital. Dr. Vahlne now serves as a senior professor at Karolinska Institutet and is the director of the Karolinska GVN center of excellence. Dr. Vahlne obtained his medical doctoral degree and license to practice medicine from the Gothenburg in 1973 and his Ph.D from the same University in 1978. He is a certified specialist in Clinical Virology since 1978. In 1982-83 he spent a sabbatical at Scripps Clinic and Research Foundation in La Jolla on a Fogarty Fellowship.

From 1972 to 1986 Dr. Vahlne’s research focused around the neuro-pathogenesis of herpes simplex virus infections. He thereafter switched to mainly work on human lentiviruses, in particular HIV. Dr. Vahlne is a member of the President’s Advisory Board for the National Virus Reference Laboratory at the University College Dublin since 2010.

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Scott C. Weaver, M.S., Ph.D. Director, Institute for Human Infections and Immunity. Scientific Director, Galveston National Laboratory. John Sealy Distinguished University Chair in Human Infections & Immunity. Dr. Weaver is a virologist and vector biologist who advances our understanding of arthropod-borne viruses (arboviruses), their transmission by mosquitoes, and develops vaccines to control the diseases that they cause. As a faculty member at the University of Texas Medical Branch (UTMB) since 1994, he has developed an internationally recognized research program encompassing the ecology and epidemiology of enzootic arbovirus transmission cycles, virus-mosquito

interactions, and emergence mechanisms of epidemic strains. Dr. Weaver utilizes his broad training to develop interdisciplinary approaches that have had major impacts on our understanding of arboviral disease emergence. These include Venezuelan equine encephalitis, for which the international research groups he has led determined the ecological and evolutionary sources as well as mechanisms of epidemic strain emergence. Dr. Weaver’s recent studies have focused on chikungunya virus, its history of emergence from wildlife African cycles, mosquito-adaptive evolution and its viral genetic constraints, as well as Zika virus, which arrived in the Americas and is causing a major epidemic associated with congenital microcephaly and Guillain Barré syndrome. Dr. Weaver has also developed promising new vaccines for several of these arboviral diseases. The chikungunya vaccine developed in his laboratory, licensed to Takeda Pharmaceuticals and patented in 19 countries, is in late preclinical evaluation. Dr. Weaver’s research has led to over 260 peer-reviewed publications in scientific journals, and over 70 reviews and book chapters. In 2014 he received the Walter Reed medal, awarded every three years by the American Society of Tropical Medicine and Hygiene for distinguished career accomplishments in tropical medicine research. His many leadership positions include his current role as Chair of the Global Virus Network’s Chikungunya and Zika Task Forces. He also serves as an editor for several major tropical medicine and microbiology journals.

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Dr. Lothar H. Wieler is the president of the Robert Koch Institute, the central Public Health Institution responsible for disease control and prevention in Germany. He is also a Professor at the Centre for Infection Medicine, Institute of Microbiology and Epizootics of the Freie Universität (FU) in Berlin. After obtaining his doctoral degree from the Ludwig-Maximilians-Universität Munich, he had a first Post-Doc position at the Pathology Department, Universität Ulm, and further on at the Institute of Hygiene and Infections of Animals at the Justus-Liebig-Universität, Gießen. Two sabbatical stays, a first one 1996 at the Center for Vaccine Development, University of Maryland in Baltimore, USA, the

second 2012 at the Wellcome Trust Sanger Institute, Hinxton, further inspired his research interests. Prof. Wieler has received the Young Researchers award from the German Veterinary Association and the Main Award of the German Association for Hygiene and Microbiology. His research focuses around infections caused by zoonotic agents as well as drug-resistant and multi-drug resistant bacterial pathogens. Molecular pathogenesis and risk assessment based on molecular functional infection epidemiology – utilizing latest molecular technologies - of bacterial pathogens is a discipline that has been moved ahead by him. He is author of more than 215 peer-reviewed papers. Prof. Wieler was chair of the scientific advisory committee of the Friedrich-Loeffler-Institute (Federal Research Institute for Animal Health in Germany). Since 2010 he has been an elected member of the German National Academy of Sciences Leopoldina, since 2016 Senator of the Section “Veterinary Medicine “.

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Luc Willems, research director of the belgian National Fund for Scientific Research (FNRS) and professor of molecular biology at the university of Liège (ULg). Research topics include the understanding of the mechanisms of cancer induced by viruses (HTLV and BLV) or by environmental factors (mesothelioma).http://www.giga.ulg.ac.be/cms/c_22956/fr/laboratory-of-cellular-and-molecular-epigenetics-home

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Yong-Zhen Zhang Ph.D. Department of Zoonoses, National Institute for Communicable Disease Control and Prevention, Chinese CDC, Beijing, China Dr Zhang is a professor and head of Department of Zoonoses, National Institute for Communicable Disease Control and Prevention, Chinese CDC. His department is mainly responsible for the control and prevention of Rickettsial diseases and Chlamydiosis. His major researches are about the discovery of unknown viruses, their evolution and ecology. To date, his group has identified more than 140 novel viruses (new species) including arenavirus, hantavirus, coronavirus, Chuviruses, and Jingmen viruses. Of them,

Chuviruses and Jingmen viruses will rep resent two novel families. Jingmen viruses provide the first example of a virus with a segmented genome that is at least partly derived from an unsegmented genome, while the Chuviruses exhibit various genome organizations, ranging from non-segmented to bi-segmented and circular genomes. In the phylogenetic trees, the Chuviruses fell between segmented and non-segmented viruses, and appear to provide an evolutionary link between segmented and non-segmented negative RNA viruses. The discovery of these novel viruses provides new clues about the origins of RNA viruses.

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Harry Kleanthous, Ph.D. Associate Vice President US Head of Research Sanofi Pasteur.Dr. Kleanthous has over 22 years industry experience in the research & development of recombinant live attenuated and subunit-based vaccines against viral and bacterial pathogens. He joined Sanofi Pasteur as the North American Head of Discovery Research in 2008 with responsibility for evaluating and developing novel viral vaccine platforms and delivering novel targets to the Development pipeline. Previously, Dr. Kleanthous was Vice President of Research at Acambis Inc., with responsibility for developing a new exploratory

portfolio. His research interests have been in the field of replication-defective viral vaccine platforms, targeting Flaviviruses, Papilloma and Herpes viruses, as well as their use for foreign antigen delivery. In recent years Dr. Kleanthous has focused efforts on the research and development of Broadly Protective Influenza Vaccines. Prior to joining industry, Dr. Kleanthous was a scientific investigator at academic teaching hospitals and the Central Public Health Laboratory Service in the UK, where he developed his expertise in the area of infectious diseases. He obtained his Ph.D. in the field of Molecular Microbiology from the University of London.

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CONTACT DETAILSSano Pasteur welcomes information about new partnership opportunities. Each opportunity is carefully evaluated and reviewed by our dedicated team.

Please contact:

Jean-Marc Renard, MS, MBAVice President, Corporate DevelopmentTel: +33 4 3737 3480Email: jean-marc.renard@sano pasteur.com

Sano� Pasteurwww.sano�pasteu r . com

Partnership opportunities with Sano PasteurSano Pasteur, the vaccines division of Sano , is seeking partners who will share the company’s pursuit of innovation and drive for excellence. Our diverse culture and geography allow us to collaborate effectively with a broad array of partners around the world.

W

Sano Pasteur is interested in partners who will share in the pursuit of innovation and our drive for excellence, while becoming a part of our market success story. “We welcome the opportunity to evaluate technologies related

to the development and production of human vaccines, both prophylactic and therapeutic, including vaccines for infectious and chronic diseases,” said Roman Chicz, PhD.

Sano Pasteur has a strong commitment to Research and Development partnerships with major universities, research institutes, govern-ment bodies, biotechnology companies and con-tract research organizations. The company's col-laborations cover virtually all aspects of vaccine development, including early-stage research.

Examples of current partnerships and technol-ogy investments include: vaccines for dengue fever, Japanese encephalitis, S. pneumoniae,

A company partnering with Sano Pasteur interacts with a multidisciplinary team that has years of experience in working to ensure that partnerships are executed succesfully and nur-tured for the mutual bene t of all parties.

This approach utilizes the value-added Sano

Pasteur alliance management capability, which focuses on the relationship by facilitating open communication, trust, understanding and clear expectations across the project lifespan. Combined with the technical competency of the alliance, this balance provides a well rounded environment for your technology to ourish.

Sano Pasteur is interested in potential partnering opportunities in the eld of active and passive human immunization, as well as technologies supporting product development and industrial performance, including:

Characterization and assay of immune responses and disease markersAnimal models of human diseases

Biological markers for evaluating the

interventions

In vitro models of human tissues, including the immune system

Epidemiological studies relevant to the use of vaccines and immunotherapeutics

Tools for improving vaccine and monoclonal antibody research, development and production Development and application of new technologies in the areas of genomics and proteomics

Prokaryotic or eukaryotic cell lines for antigen production

Fermentor and bioreactor technology

Disposable systems

Online testing

Process automation

Preservatives and stabilizers

Bioinformatics techniques for modeling, data handling and analysis

Anti-counterfeiting technology

Vaccines, monoclonal antibodies and supporting technologies for prevention and treatmentof infectious diseases

Novel antigens and methods for antigen discovery and characterization Carrier proteins and protein-

polysaccharide conjugation methods or alternative technologies

Vaccine vectors suitable for nasal or oral use

New ways to administer vaccines

Agents to enhance vaccine immune responsesAdjuvants and immunomodulators

Vaccine vectors and delivery systems intended to enhance or modify immune responses

Biological and immunological studies to further characterize adjuvants and immunomodulators

e are not only at the forefront of conquering newly targeted infectious diseases, but also leading the way in

expanding immunization across all age groups, including adolescents and the elderly. This leadership has translated into outstanding success in the industry, and our company has experienced a recent period of unprecedented growth.

and M. tuberculosis; pediatric combination vaccines; rabies monoclonal antibodies; large-scale, cell culture-based virus production; adjuvants and immunomodulators; conjugate vaccine production; and vaccine delivery systems.

Roman Chicz, PhDHead, External Research and DevelopmentTel: +1 617 866 4562Email: roman.chicz@sano�pasteur.comSano� Pasteur recently signed an agreement

with SK Chemical Co. of South Korea to co-develop an innovative pneumococcal conjugate vaccine

マイクロニードル（皮内投与デバイス）マイクロニードルは基盤上に数百μmサイズの微小なニードルが多数配

置されており、角質層を物理的に突破して、薬剤を皮内へ効率的に投与することが可能です。

Micro needle (Intradermal administration device)A lot of micro needles (400µm) are placed on a base. These needles break through stratum and can deliver a drug into skin effectively.

その技術は人のために。Your Partner in Health Car.

医薬品、医療機器に関するワンストップサービスの実現Actualization of One Stop Service in relation to Pharmaceutical & Medical Equipment

医薬品保存

Preservationof drug

医薬品調製

Dispensing of drug

医薬品製造

Manufacturing of drug

医薬品投与

Administration of drug

噴霧投与デバイス＜特徴＞バイアルからの移注タイプ、PFSタイプの設計が可能使用者に左右されない均一な粒子径及び一定量の噴霧を１つのシリンジで複数回おこなえます。例）ワクチン等、製剤の噴霧投与

Liquid Spraying Administration device (Multi dose type) <Feature>We can propose two types of this device . One type is a transfusion from a vial and the other type is a pre filled syringe.This device can perform a regular size of liquid particle and an aliquot of liquid spraying not to depend on an user. ex) Vaccine, Liquid spraying administration for drug

ネストシリンジネストシリンジとはReady‐to‐Fill包装（製薬メーカーにおいて洗浄、滅菌工程無しで充填が可能な包装形態）のシリンジである。・材質 ガラス & COP ・種類 ルアースリップ、ルアーロック、針付

Nest syringeNest syringe means that there are a lot of syringes of Ready-to-Fill-Packaging (Pharmaceutical company can use these without the process of washing and sterilization)・Material : Glass & COP ・Type : Lure slip, Lure lock, with needle

ニプロ株式会社 医薬事業部 URL: http://www.nipro.co.jp(大阪) 〒531-8510 大阪市北区本庄西3丁目9番3号 TEL06-6375-7609(ダイヤルイン) FAX 06-6375-9050

E-mail：DDS-info@nipro.co.jp