2^nd International conference on Flu November 01-02, 2016 San Francisco, California, USA

Biography:

Anthony S Gilbert has obtained his Bachelor of Medicine and Bachelor of Surgery degree from the University of the Witwatersrand, South Africa. He is a Member of the Institute of Clinical Research. He has served as an expert Member and Vice Chair of a National Research Ethics Service (NRES) committee, having been appointed by the Health Research Authority in the U.K. As a Principal Investigator, he has supervised and conducted viral challenge studies in order to further the quest to bring safer and more effective vaccines and antivirals to the global community. His research has been published in several medical and scientific journals, including Nature Medicine.

Abstract:

Since the beginning of the millennium, human viral challenge studies have successfully been conducted at hVIVO to develop a series of well-characterized virus stocks, whilst demonstrating that the Human Viral Challenge Model (HVCM) could be effective in offering clients a faster and cost effective route to market for their therapeutics. The Human Viral Challenge Model enables global pharmaceutical and biotechnology companies, as well as leading academic groups and government institutions, to undertake scientific research, accelerate the drug development timeline and reduce the cost of bringing antiviral drugs, vaccines and diagnostics to market. The HVCM also enables fundamental research into the human response to infection and crucial research into modes of infection and transmission between individuals in the community. As hVIVO has grown and developed, the HVCM has become widely accepted as an alternative to traditional early stage field trials to show the efficacy of antiviral and vaccine therapeutics in Influenza, Respiratory Syncytial Virus (RSV) and Human Rhinovirus (HRV). By monitoring the entire disease lifecycle as subjects move from healthy to sick and recover back to healthy again, we can obtain high quality, longitudinal data from the before, during and after phases of disease. The model can be used to study the efficacy of new therapies and also to study the target disease itself.

Biography:

Manon M.J. Cox, MBA is President and Chief Executive Officer of Protein Sciences. Dr. Cox has received many honours and awards recognizing her stature as a leader in innovation and influenza including receiving a Doctorate in Humane Letters honoris causa from St. Joseph University and in 2015 elected fellow of the International Society of Vaccines. Dr. Cox holds a Doctorate from the University of Wageningen, received her MBA with distinction from the University of Nijenrode and the University of Rochester, NY and holds a Doctorandus degree in Molecular Biology, Genetics and Biochemistry from the University of Nijmegen, The Netherlands.

Abstract:

Flublok is FDA approved for the prevention of influenza in adults 18 and older. Flublok is the first recombinant hemagglutinin influenza vaccine and is produced using the baculovirus-insect cell technology. This production platform provides an attractive alternative to the current egg-based influenza vaccine manufacturing process for a multitude of reasons including speed, scale-ability, cost and independence on eggs. The key advantage of this recombinant protein manufacturing platform is that a universal “plug and play” process enables manufacturing of new vaccine candidates within a matter of months while offering the potential for low manufacturing costs. Globally large scale mammalian cell culture facilities previously established for the manufacturing of monoclonal antibodies could be deployed for the manufacturing of vaccines in the event of an emergency or alternatively, manufacturing capacity could be established in geographic regions that do not have any vaccine production capability. Dependent on health care priorities, different vaccines could be manufactured in such facilities while maintaining the ability to rapidly convert to producing pandemic influenza vaccine when the need arise. The speaker will provide an update on the global manufacturing capacity established specifically for Flublok and present recently obtained comparative efficacy data demonstrating that Flublok is more effective than tradional vaccine in protecting older adults against mismatched influenza viruses. Acknowledgment: Protein Sciences Corporation was awarded a contract in June 2009 from the U.S. Department of Health and Human Services to further develop this technology for the production of recombinant influenza vaccines for pandemic preparedness.

Biography:

Tracey Goldstein, PhD, is Associate Director and Professor at the University of California Davis, One Health Institute, where she developed and oversees the One Health Institute Laboratory and the Marine Ecosystem Health Diagnostic and Surveillance Laboratory. She is also the Co-PI and Pathogen Diagnostics Co-Lead for the viral emergence early warning project PREDICT, developed with the US Agency for International Development’s Emerging Pandemic Threats (EPT) Program.

Abstract:

Surveillance has shown aquatic birds, particularly migrating waterfowl, to be reservoirs for nearly all of the currently recognized Influenza A viruses. Recently traditional and diverse Influenza A viruses have been detected in bats and other species such as seals, suggesting multiple species may play a role in transmission and emergence. A broader surveillance approach has led to an increased detection of animal-origin infections in humans following animal contact. We performed a retrospective analysis of available influenza A sequences examining high-priority animal-origin subtypes between 2000 and 2011 from 32 different countries to identify trends in evolutionary dynamics to better understand where novel strains may next emerge and to identify data gaps in knowledge due to reporting effort. As part of ongoing surveillance under the USAID funded Predict project, we also performed global screening of samples from diverse hosts including bats and rodents globally, and through joint surveillance with NOAA and NIAID we screened for influenza A viruses in marine mammals off the Pacific coast of the United States from Alaska to California. Retrospective analyses indicated that mutation rates were higher in Asian countries, particularly in East Asia. Diverse influenzas were detected in new hosts and locations, including in bats in South America and Africa, rodents in Asia, and human and avian-origin influenzas were detected in seals off California. Finally, we identified major global gaps in influenza reporting and in broad subtype testing which will continue to hinder efforts to track the evolution and diversity of Influenza A viruses around the world.

Biography:

K. Kai McKinstry completed his PhD at the University of Saskatchewan in 2005 and pursued postdoctoral studies at the Trudeau Institute in Saranac Lake, NY. He joined the Faculty of the Department of Pathology at the University of Massachusetts Medical School in 2010. In 2015, Dr. McKinstry was recruited to the Burnett School of Biomedial Sciences at the University of Central Florida.

Abstract:

Tissue-resident memory T cells (TRM) are thought to play a key role in protective recall responses against pathogens. TRM subsets that persist at sites of previous infection may be especially important for immunity against pathogens such as influenza A virus (IAV) that can evade neutralizing antibodies. How TRM cells form during immune responses is not fully understood, especially for CD4+ T cells. We recently found that virtually all memory CD4 T cells that develop in secondary lymphoid organs following IAV priming require autocrine IL-2 signals. Here, we describe a unique role for IL-15 in supporting the generation of a subset of IL-2-independent lung CD4+ TRM cells formed during IAV priming. Our results demonstrate that this TRM subset is highly functional and can more efficiently elicit pro-inflammatory responses from dendritic cells presenting cognate peptide antigen than can conventional splenic memory CD4 T cells expressing the same T cell receptor. We have previously shown that this function correlates with initial control of viral titers during the first few days following IAV challenge. These studies, identifying a novel role for IL-15 in specifically supporting the priming of a subset of lung CD4 TRM cells with specialized function are highly relevant to vaccine design.

Biography:

Thomas Voss, Ph.D., is a world-renowned thought leader in infectious disease research, and has deep expertise in virology, immunology, biodefense, and vaccine and antiviral development. His research interests include cell-virus interactions and their role in the pathogenesis of acute viral infections, as well as therapeutic and vaccine development. Voss joined SRI in 2013 from the Tulane School of Medicine’s Department of Microbiology and Immunology, where he was an associate professor from 2005 to 2012. From 1998 to 2005, he worked in various roles at Southern Research Institute, ultimately as vice president of the Homeland Security and Emerging Infectious Disease Division. Previously, Voss held roles at Carl Zeiss, Inc. (Advanced Imaging Microscopy group), the U.S. Centers for Disease Control and Prevention (Measles Virus Section, Respiratory and Enteric Virus Branch), and University Hospital in Zurich, Switzerland (Internal Medicine Division).

Abstract:

TBA

Biography:

Giulio Filippo Tarro has graduated from Medicine School, Naples University in 1962. He is the President Foundation de Beaumont Bonelli for Cancer Research. His basic researches have been concerned with antigens induced early during the replication cycle of human herpes viruses. Another study has involved the identification, isolation and characterization of specific virus-induced tumor antigens, which were the fingerprints left behind in human cancer. He is the recipient of the Sbarro Health Research Organization Lifetime Achievement Award in 2010. His achievements include patents in field of discovery of Respiratory Syncytial Virus in infant deaths in Naples and of tumor liberated protein as a tumor associated antigen, 55 kilo Dalton protein overexpressed in lung tumors and other epithelial adenocarcinomas.

Abstract:

Since the emergence of a novel aquatic bird Flu agent in humans may be detected in near future, approaches to early diagnosis and prompt therapy are welcome. The swine-origin influenza virus (S-OIV) detected in April 2009 in Mexico, Canada and USA exhibited an unique genome composition not shown before. The emerging new Flu agent can cause outbreaks of febrile respiratory infection from mild to severe diseases throughout the world. This summary has the purpose to emphasize the possibility of tracking the new influenza virus in the most affected regions of the world and to avoid a sad toll flu-related deaths that might occurre. The possible causes of high incidence and mortality rates are going to be discussed as well as their implications on the public opinion and the prevention campaign.

Biography:

Jun Wang is Assistant Professor in Pharmacology & Toxicology department, University of Arizona, Arizona. He is awarded with PhD in Chemistry from University of Pennsylvania in 2010. He completed his MS in Chemistry from National University of Singapore, Singapore in 2006 followed by BS Chemistry from Wuhan University, China in 2003.

Abstract:

Each year more people die of flu-related illness than breast cancer, which places influenza virus infection the top ten leading causes of deaths in the U.S. In addition, sporadic and unpredictable influenza pandemics cause even more devastating damages to public health and global economy. Despite this grand challenge, we are limited by the therapeutic countermeasures against flu infection. The only class of drugs that remains effective is the viral neuraminidase inhibitors (NAs), such oseltamivir, zanamivir, and peramivir. However, like many other drugs used to treat infectious diseases, NAs are not an exception in terms of drug resistance, and flu viruses that are resistant to NAs have been continuously reported. Thus this is a pressing need to develop antivirals to combat multi-drug resistant influenza A viruses. Towards this goal, we explore the influenza A virus M2 proton channel as the drug target. Specifically, we focused on the M2-S31N mutant, which is the predominant drug-resistant mutant among current circulating influenza A viruses. Using an integrated approach involving molecular dynamics simulations, NMR, X-ray, electrophysiology, virology, and medicinal chemistry, we were able to design the first-in-class M2-S31N inhibitors. These lead compounds are not only potential drug candidates, but also invaluable chemical tools which enable us to address fundamental questions such as: Are M2-S31N inhibitors active against multi-drug resistant influenza A viruses? how is the genetic barrier of drug resistance of M2-S31N inhibitors compared to amantadine? Will mutant viruses similarly evolve resistance to M2-S31N inhibitors? If resistance were to emerge, what is the mechanism? Answers to these questions are pivotal to advance the drug discovery program forward. 

Biography:

Tara M. Strutt received her PhD from the Department of Microbiology and Immunology at the University of Saskatchewan. Her studies focused on the signals required to activate CD4 T cells during immune responses. Dr. Strutt continued to study CD4 T cells during her postdoctoral studies at the Trudeau Institute in the laboratory of Dr. Susan L. Swain. While at the Trudeau Institute, Dr. Strutt uncovered novel protective functions mediated by memory T cells during influenza virus infection and that different protective functions are mediated by memory cells in different organs. In 2010, Dr. Strutt relocated to the University of Massachustts Medical School as an Instructor faculty member of the Department of Pathology. Her research focus centered on understanding how the tissue environment dictates T cell function, and on defining how the adaptive immune system can control innate inflammatory responses. In 2015, she started her own independent research laboratory within the Immunity and Pathogenesis Division of the Burnett School of Biomedical Sciences in the College of Medicine at the University of Central Florida where she is continuing to study how adaptive immune responses regulate innate immunity.

Abstract:

The primary goal of vaccination is to protect individuals from the morbidity and mortality of pathogen exposure by generating immunological memory. Our current understanding is that memory CD4 T cells, commonly regarded as the regulators of memory cytotoxic CD8 T cells and/or antibody-producing B cells, provide protection by hastening pathogen clearance through ‘faster, bigger, and better’ immune responses. It is now clear, however, that many different subsets of CD4 T cells, many with specialized functions other than providing ‘help’, are generated during immune responses against pathogens. In studies designed to ascertain the full functional potential of memory CD4 T cells responding against influenza A virus (IAV), we found that virus induced TH1-like, as well as in vitro polarized TH1 or TH17 memory CD4 T cells, enhance early innate inflammatory responses that correlate with better and earlier control of IAV in infected lungs. In further studies, we found innate lymphoid cells (ILC), which are not normally associated with anti-viral responses but rather associated with healing and wound repair, are also mobilized by memory CD4 T cells during the early stage of the response against IAV. Unexpectedly, the protection afforded by memory CD4 T cells against lethal IAV challenge is significantly compromised when ILCs are depleted. These findings reveal a previously unappreciated beneficial role of memory CD4 T cells in regulating tissue homeostasis during recall responses against pathogens through the regulation of ILC subsets.

Biography:

Tara M. Strutt received her PhD from the Department of Microbiology and Immunology at the University of Saskatchewan. Her studies focused on the signals required to activate CD4 T cells during immune responses. Dr. Strutt continued to study CD4 T cells during her postdoctoral studies at the Trudeau Institute in the laboratory of Dr. Susan L. Swain. While at the Trudeau Institute, Dr. Strutt uncovered novel protective functions mediated by memory T cells during influenza virus infection and that different protective functions are mediated by memory cells in different organs. In 2010, Dr. Strutt relocated to the University of Massachustts Medical School as an Instructor faculty member of the Department of Pathology. Her research focus centered on understanding how the tissue environment dictates T cell function, and on defining how the adaptive immune system can control innate inflammatory responses. In 2015, she started her own independent research laboratory within the Immunity and Pathogenesis Division of the Burnett School of Biomedical Sciences in the College of Medicine at the University of Central Florida where she is continuing to study how adaptive immune responses regulate innate immunity.

Abstract:

It is generally accepted that the flow of immunologically relevant information during the early stages of responses against pathogens is one-way, - that inflammation induced upon pattern recognition by highly conserved receptors of the innate immune dramatically impacts subsequent antigen-specific T and B cell responses.  We asked if the reverse occurs, and if cells of the adaptive immune system can influence the character and magnitude of innate inflammatory responses.  We show here that resting, antigen-specific memory CD4 T cells can dramatically alter innate inflammatory responses within 36 hours of viral infection in a manner independent of other T cells and TLR signaling.  Virus-specific memory CD4 T cells transferred to naïve mice that are then challenged with influenza induce greater expression of multiple inflammatory mediators both at the site of infection and systemically upon cognate recognition of antigen in an IFN-gindependent fashion.  Our results show that the adaptive immune system can profoundly influence the character of inflammation following pathogen challenge, demonstrating a novel role for memory CD4 T cells in controlling virus titers during protective.

Biography:

Phillip B. Berkey Moheno holds a BS and a Candidate in Philosophy in Biochemistry from the University of California, Los Angeles, and a PhD in Confluent Education from the University of California, Santa Barbara. In addition he has more than 20 years of research experience into the anti-cancer properties of pterins. He has published 12 papers in reputed journals.

Abstract:

Calcium Folate is the excess calcium salt of the vitamin folic acid. Folic acid is sensitive to acidic-oxidative conditions and, in the presence of excess Ca+2 as well, is transformed into pterins and calcium pterins. This pilot observational study describes the use of CaFolate-derived calcium pterin 6-carboxylate in the treatment of certain immune-related ailments. Patients with various immune-associated disorders were directed to take ad libitum 25-76 mg of CaFolate (300-900 µg folic acid equivalent) orally per day, as an adjuvant therapy, and to collect personal and medical assessments. The users reported no flu/colds (>20/20 reporting none during the cold and flu season), greater energy/stamina (8/8 reporting increased), less osteoarthritis pain (10/11 reporting improvement), diminished mouth sores due to chemotherapy (2/2 reporting significant clearance), and cancer remissions (4/5 reported plus 1 transient improvement in a terminal case). These observational findings identify certain clinical endpoints for future matched group, randomized, double-blind, placebo-controlled clinical trials. One such clinical trial is underway in osteoarthritis.

Biography:

Donald Pinkston Francis, completed undergraduate studies at the U.C. Berkeley, received his M.D. from Northwestern University and his Doctor of Science in Virology from Harvard. He joined CDC in the early 1970s, where combated smallpox, cholera, Ebola and AIDS. His early work on HIV/AIDS was chronicled in Randy Shilts? And the Band Played On. From 1988 to 1992, he was Special Consultant on AIDS to San Francisco Mayor Art Agnos. After retiring from CDC in 1992 he worked on HIV vaccines at Genentech, VaxGen and now a not-for-profit company GSID.

Abstract:

In recent years, there have been dramatic changes in both the supply of existing vaccines and early stage development of new vaccines. There have been shifts that have seen vaccine companies from Brazil, India and China taking larger and larger roles in both the development and production. From the vaccine production/supply side, companies from emerging markets supplied less than 10% of UNICEF purchased vaccines in 1997. That increased to about 50% by 2012. From the vaccine development side, some of these companies have undertaken major projects for the development of new products for diseases as disperate as malaria, dengue, human papiloma virus, influenza and Japanese encephalitis. The movement of these vaccines from early development, to local licensure and then to UNICEF prequalification, bodes well for the health of the world.

Biography:

Shan Lu is professor of medicine and biochemistry & molecular pharmacology, has been elected president of the International Society for Vaccines (ISV). He is a physician-scientist, is a pioneer in the field of DNA vaccines and has conducted extensive research on AIDS vaccines, as well as vaccines against emerging infectious disease and biodefense targets.

Abstract:

TBA

Biography:

Nicolas Noulin has completed his PhD in Immunology and Molecular Biology from Orleans University (France) and Post-doctoral studies from Institut Pasteur in Paris. He is a Principle Virologist at hVIVO, a company pioneering a technology platform which uses human models of disease.

Abstract:

TBA

Biography:

Tony Velkov has completed his PhD from Monash University, Australia in 2000. His research focus is in the field of anti-infective discovery. He was awarded a National Health and Medical Research Council (NHMRC) Research Fellowships in 2006, 2011 and 2015. The quality and impact of his independent research was recognized by the NHMRC with an Excellence Awards in 2011 and 2015. He has published over 70 papers in high caliber journals and 5 book chapters.

Abstract:

Influenza is a constant global burden to human health. In order to evolve from its avian form and gain the pandemic potential for increased transmissibility between humans, the hemagglutinin (HA) of avian influenza viruses will need to undergo mutations in its receptor binding site (RBS) that bring about an avian to human receptor preference switch. In order to understand the major determinants of virus transmissibility and the pandemic potential of the novel avian influenza viruses we have determined the crystallographic structure of the novel avian influenza H10N7 A/Turkey/MN/3/79 to 1.96Å and mapped the RBS. The amino acid residues responsible for conferring receptor selectivity were identified by site direct mutagenesis of recombinant H10 HA proteins. The receptor binding selectivity of the HAs was determined using sialyl glycan binding assays. Docking models were constructed of the H10 HA in complex with α2,6-sialic acid (human) and α2,3-sialic acid (avian) pentasaccharide receptor analogs to ascertain the correlation between the binding assay data and the interactions within the receptor binding pocket. The presented findings provide a structure recognition perspective for the receptor binding properties of the novel avian H10 influenza HA.

Biography:

Zheng Li has completed his PhD at the age of 31 years from Xi'an Jiaotong University and postdoctoral studies from German Cancer Research Center. He has published more than 27 papers in reputed journals in the last five years.

Abstract:

Recent studies have elucidated that expression of certain glycoproteins in human saliva are increased or decreased according to age, meanwhile, human saliva may inhibit viral infection and prevent viral transmission. We find that seven lectins (e.g., MAL-II and SNA) show significant age differences among children, adults, and elderly individuals. Interestingly, we observe that healthy elderly individuals have the strongest resistance to influenza A virus mainly by presenting more terminal α2-3/6-linked sialic acid residues in their saliva, which bind with the influenza viral hemagglutinations. However, it is often noted that hospitalizations and deaths after an influenza infection mainly occur in the elderly population living with chronic diseases, such as diabetes and cancer. We find that the expression level of the terminal α2-3-linked sialic acids of elderly individuals with type 2 diabetes mellitus and liver disease are down-regulated significantly, and the terminal α2-6 linked sialic acids are up-regulated slightly or had no significant alteration. But, in the saliva of patients with gastric cancer, neither sialic acid is significantly altered. These findings may reveal that elderly individuals with chronic diseases, such as diabetes and liver disease, might be more susceptible to the avian influenza virus due to the decreased expression of terminal α2-3-linked sialic acids in their saliva.Our findings imply that the expression level of terminal α2-3 or α2-6-linked sialic acids in human saliva is a risk factor that could be a biomarker to distinguish those patients who are at a greater risk for infection with the avian or human influenza viruses.

Biography:

Wen Tian Chen has completed his PhD from Northwest University in China. He is a Lecturer in Northwest University. He has published more than 5 papers in reputed journals.

Abstract:

We undertook a detailed investigation of the distribution and the evolutionary pattern of the potential glycosites (N-glycosylation site) in the envelope glycoproteins of Influenza Virus. Two glycosites were located at HA0 cleavage sites (e.g., the 27N in H1) and fusion peptides (e.g., the 498N in H1) and were strikingly conserved in all HA subtypes. Two to four conserved glycosites were found in the stalk domain of NA, but these are affected by the deletion of specific stalk domain sequences. Another highly conserved glycosite (e.g., the 146N in N2) appeared at the top center of tetrameric global domain, while the others glycosites were distributed around the global domain. We further focus on the H5N1 virus and conclude that the glycosites in H5N1 have become more complicated in HA and less influential in NA in the last seven years. Two glycosylation sites, 158N and 169N, which located near to the receptor-binding domains (RBDs) of HA, also participated in receptor recognition. We attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA(Sialic Acid)-a-2,3-Gal(Galactose) and SA-a-2,6-Gal sialoglycan adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-a-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-a-2,3-Gal analogs.

Biography:

Ilya B Tsyrlov has completed his PhD from Novosibirsk University and Postdoctoral studies from Leningrad Academy of Medical Sciences. He is the President and Chief Scientific Officer of XENOTOX, Inc., an American premier biomedical innovation organization. He has published 4 monographs and about 250 papers in reputed journals and has been serving as an Editorial Board Member of several journals.

Abstract:

Cognate DRE sites within DNA enhancer epitomizes wide range of mammalian genes expression mediated via the Ah receptor pathway. Earlier we postulated the same for DRE-containing viral genes transactivation caused by dioxin in human cells infected with HIV-1, HBV and hCMV. Here, such mechanistic concept applied to type A influenza virus NS1 binding protein in human and avian (G. gallus gallus) host cells. The NS1 is known to prevent transcriptional induction of antiviral interferons to inhibit splicing and dsRNA-mediated signal transduction in target cells. Presenting data range from the cellular to population levels. It was shown that gene encoding the NS1 possessed multiple DREs (core nucleotide sequence 3' A-CGCAC 5'), two of which were identified within the promoter area, namely at positions -7942 and -687. SITECON, an established computational tool for detecting transcriptional factor binding site recognition, proved the above sites as potentially active. SITECON-selected adjacent variable sequences were used to detect properties of the DRE site and conformational similarity score threshold of 0.95 was utilized to rank identified DRE. On the cellular level, Western blot analysis of lysates of infected or DNA-transfected confluent HeLa cells pretreated with 10 ppt dioxin for 36 h revealed several-fold increase of NS1-specific polypeptide. As the NS1 promoter contains two potentially active DRE, an extrapolation from the data on HIV-1 (1 DRE) and hCMV (10 DRE) also suggests that concentration of dioxin up-regulating NS1 gene should be moderately above current dioxin levels in general population (~ 4 ppt). Presumably, elevated dioxin level in the host cells might lead to enhanced ability of NS1 to diminish antiviral interferons. That can bring new insights to the fact that resistance of highly virulent H5N1 to antiviral effects of IFN-β and TNF-α directly associated with the NS1. On the population level, the data on wild birds and domestic poultry (G. gallus gallus) dying from H5N1 in Guangdong province of China and Long An, Tieng Giang and Ben Tre provinces of Vietnam, all relate to the fact that water and soil in these regions are highly contaminated with dioxin-like compounds. Eventually, human cohorts from the above regions of China and Vietnam are exposed to elevated concentrations of dioxin, which might serve as a promotional factor for seasonal influenza outbreaks. Moreover, the sub-nanomolar body burden dioxin might strongly facilitate spreading of the H5N1 in case avian flu pandemic were to occur.

Biography:

Diane Beylkin graduated with honors from Caltech in 2010 with a B.S. in chemistry. She recently completed her PhD at Yale University in the laboratory of Dr. Andrew Phillips working on the total synthesis of thailandamide A. She is currently conducting her postdoctoral research on the influenza virus at SRI International in the laboratory of Dr. Thomas Webb.

Abstract:

Influenza is an infectious disease responsible for up to 500,000 deaths worldwide annually despite the availability of vaccines and antiviral drugs. Vaccines target the most common strains of the virus, leaving those exposed to other strains at risk for infection. Most small molecule antiviral drugs currently on the market act as neuraminidase inhibitors (zanamivir, oseltamivir, peramivir) or target the M2-ion channel (amantadine, rimantadine); however, due to the lack of viral proof-reading enzymes, these targets are prone to rapid mutations that often confer antiviral resistance. In contrast, the viral RNA-dependent RNA polymerase (RdRp) is an attractive drug target because it is relatively slow to develop drug resistance, conserved across genotypes, and essential to viral replication. With no eukaryotic homologue, the potential for toxicity due to off-target effects is low for RdRp targeting compounds. Our research focuses on targeting the endonuclease domain of the RdRp, located on the PA N-terminal domain, which has a two metal binding active site. We have developed a series of 2-substituted dihydroxypyrimidine carboxamides which bind to the endonuclease active site and disrupt its activity in vitro. The activity of these compounds has been validated by fluorescent polarization binding assays and plaque inhibition assays. The most potent inhibitors have been co-crystallized with PAN to determine the structure-activity relationships, allowing us to improve their efficacy. We will discuss the structure-activity relationship of our analogs and several interesting protein-small molecule X-ray crystal structures, as well as our progress on the development of an innovative therapeutic lead compound targeting influenza endonuclease.

Biography:

Gyanendra Kumar has earned his PhD from IISc, Bangalore in 2007 and then joined the Brookhaven National Laboratory, New York and worked on drug discovery for Botulinum neurotoxins. Currently, he is a Postdoctoral Research Associate at the Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, working on the drug discovery for influenza by targeting the endonuclease domain of viral RdRp. He has published numerous research articles on malaria, botulism and influenza and presented his work at international conferences. He serves as a Referee for several journals and is a Member of ACS, ACA, AAAS and ISIRV.

Abstract:

The influenza endonuclease is an essential sub-domain of the viral RNA polymerase. It processes host pre-mRNAs to serve as primers for viral mRNA and is an attractive target for anti-influenza drug discovery. Compound L-742,001 is a prototypical endonuclease inhibitor, and we found that repeated passaging of influenza virus in the presence of this inhibitor did not lead to the development of resistant mutant strains. Reduced sensitivity to L-742,001 could only be induced by creating point mutations via a random mutagenesis strategy. These mutations mapped to the endonuclease active site where they can directly impact inhibitor binding. Engineered viruses containing the mutations showed resistance to L-742,001 both in vitro and in vivo, with only a modest reduction in fitness. Introduction of the mutations into a second virus also increased its resistance to the inhibitor. Using the isolated wild-type and mutant endonuclease domains, we used kinetics, inhibitor binding and crystallography to characterize how the two most significant mutations elicit resistance to L-742,001. These studies lay the foundation for the development of a new class of influenza therapeutics with reduced potential for the development of clinical endonuclease inhibitor resistant influenza strains.

Biography:

Periolo Natalia has completed his PhD at the age of 31 years from Quilmes University, buenos Aires, Argentina.She had a International Fellowship postdoctoral from the Department of Immunology, The Wenner-Gren Institute, Stockholm University. Actually, she is researcher of The National Scientific and Technical Research Council (CONICET) and work at the Institute INEI-ANLIS "Carlos G. Malbran", Argentina. She has published more than 10 papers in reputed journals.

Abstract:

Pregnant women are at increased risk for severe illness from influenza virus infection. Immunological and hormonal alterations place women at increased riskfor influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09infection resulted in increased disease severity in pregnant women, the precise mechanisms responsiblefor this risk have yet to be established. During the 2009 H1N1 influenza A pandemic, pregnant women were generally at increased risk for severe disease, including disease leading to hospitalization, admission to an intensive care unit, or death, as compared with nonpregnant women and the general population. In Argentina, it was estimated that the mortality rate per 100,000 person-years (py) ranged from 1.5 among persons aged 5–44 years to 5.6 among persons aged ≥65 years. An analysis of 332 case fatalities infectedwith A(H1N1)pdm09 virus showed that twenty (6%) were among pregnant or postpartum women of who monly 47% had been diag-nosed with comorbid disorders .Studies have demonstrated that the over-production of specific inflammatory cytokines, such as the tumor necrosis factor (TNF)-,interleukin (IL), IL-6 and IL-10, as well as the polymorphonuclearneutrophil CC chemokine- IL-8, is the hallmark of viral infection. In an attempt to elucidate the innate immune response to A(H1N1) pdm09 infection and to gain further insight into cytokine-mediated pathogenesis, we retrospectively evaluated the expression levels of a panel of cytokines, chemokines, and viral replication in different groups of pregnant women according to the severity of the infection.

Biography:

Jennifer M Reiman is an Immunologist with expertise in infectious diseases and cancer. She is interested in reducing the spread of infectious diseases such as respiratory viruses, particularly influenza. Her research is aimed at finding easy and cost-effective interventions to reduce respiratory virus transmission including the possibility of humidification during dry (low humidity) winter conditions in temperate climates such as Minnesota, USA. She is also involved in science education partnerships with schools (pre-K through middle school) through Integrated Science Education Outreach (InSciEd Out) a non-profit based within the Center for Clinical and Translational Science and Department of Biochemistry and Molecular Biology at the Mayo Clinic in Rochester, MN.

Abstract:

Statement of the Problem: Annual influenza epidemics are responsible for 250000- 500000 deaths worldwide. Preschool and elementary school classrooms represent a significant source of influenza. There is a need for cost effective interventions that reduce influenza and respiratory illnesses in classrooms.

Methodology: Study was conducted at Aldrich Memorial Nursery School, Rochester, MN (a preschool with students aged 2-5 years) from January 2016-March 2016. Classrooms of identical design each with their own HVAC system for air handling were utilized. Two classrooms had humidifiers (DriSteem) installed and were compared to two non-humidified classrooms (control rooms) with similar aged students. Data on outdoor and classroom temperatures and relative humidity was gathered to calculate absolute humidity. Air samples were collected using NIOSH samplers. Fomites were collected from objects (e.g., markers, wooden blocks) wrapped in 25% cotton linen paper that students interacted with. Paper and air samples were further processed to determine infectivity (in cell culture) or viral RNA presence and quantity by qRT-PCR.

Conclusion & Significance: Absolute humidity from January 25-March 11, 2016 for outdoors as well as indoor classroom environments is depicted. With humidification we were able to maintain elevated absolute humidity at an average of 9.89 mb compared to 6.33 mb in control rooms (1/25/16-2/23/16). Humidifiers were turned off after sample collection on 2/23/16 as ambient humidity had increased in control rooms approaching that of humidified rooms. Additionally, we investigated if there were differences in the amount of influenza A RNA in positive samples. We quantitated the NS1 gene copy number and compared samples to our standard curve with known copy numbers of the gene. The median copy number between the two groups (humidified versus controls) was statistically significant for both paper (P= 0.043, t=2.123) and air (P=0.032, t=2.435).

Biography:

Jennifer M Reiman is an Immunologist with expertise in infectious diseases and cancer. She is interested in reducing the spread of infectious diseases such as respiratory viruses, particularly influenza. Her research is aimed at finding easy and cost-effective interventions to reduce respiratory virus transmission including the possibility of humidification during dry (low humidity) winter conditions in temperate climates such as Minnesota, USA. She is also involved in science education partnerships with schools (pre-K through middle school) through Integrated Science Education Outreach (InSciEd Out) a non-profit based within the Center for Clinical and Translational Science and Department of Biochemistry and Molecular Biology at the Mayo Clinic in Rochester, MN.

Abstract:

Statement of the Problem: Annual influenza epidemics are responsible for 250000- 500000 deaths worldwide. Preschool and elementary school classrooms represent a significant source of influenza. There is a need for cost effective interventions that reduce influenza and respiratory illnesses in classrooms.

Methodology: Study was conducted at Aldrich Memorial Nursery School, Rochester, MN (a preschool with students aged 2-5 years) from January 2016-March 2016. Classrooms of identical design each with their own HVAC system for air handling were utilized. Two classrooms had humidifiers (DriSteem) installed and were compared to two non-humidified classrooms (control rooms) with similar aged students. Data on outdoor and classroom temperatures and relative humidity was gathered to calculate absolute humidity. Air samples were collected using NIOSH samplers. Fomites were collected from objects (e.g., markers, wooden blocks) wrapped in 25% cotton linen paper that students interacted with. Paper and air samples were further processed to determine infectivity (in cell culture) or viral RNA presence and quantity by qRT-PCR.

Conclusion & Significance: Absolute humidity from January 25-March 11, 2016 for outdoors as well as indoor classroom environments is depicted. With humidification we were able to maintain elevated absolute humidity at an average of 9.89 mb compared to 6.33 mb in control rooms (1/25/16-2/23/16). Humidifiers were turned off after sample collection on 2/23/16 as ambient humidity had increased in control rooms approaching that of humidified rooms. Additionally, we investigated if there were differences in the amount of influenza A RNA in positive samples. We quantitated the NS1 gene copy number and compared samples to our standard curve with known copy numbers of the gene. The median copy number between the two groups (humidified versus controls) was statistically significant for both paper (P= 0.043, t=2.123) and air (P=0.032, t=2.435).

Biography:

Andrew C.Y. Lee is a PhD candidate in the Department of Microbiology, The University of Hong Kong. My research focuses on the pathogenesis of avian influenza A H7N9 virus.

Abstract:

Following the 2013 outbreak of human infection with avian influenza A H7N9 virus, sporadic human infections have continued to occur in China. To better understand the mechanisms as how H7N9 virus causes severe illness in human, we infected human PBMCs with H7N9 (A/Anhui/1/2013) and compared to H5N1 (A/VNM/1194/2004) and 2009 pandemic H1N1 (A/HK/415742/2009) viruses. We found that H7N9 virus was as infectious as H5N1 virus to PBMCs, with large proportion of cells expressing viral antigen at 12 hours after inoculation with 2 M.O.I of each viruses, while pH1N1 infected much less of cells. Moreover, our results showed that H7N9 induced cytokine responses that were similar to that of H5N1, but different from that of pH1N1. Result of multi-color flow cytometry indicated that all three viruses were able to infect multiple cell types including CD14+ monocytes, CD4+ T cells, CD8+ T cells and CD19+ B cells. Among different cell types, CD14+ monocytes were highly susceptible to both H7N9 and H5N1 infection but less susceptible to pH1N1 infection. Surprisingly, we found that H7N9 and H5N1 virus infection caused CD14+ monocytes quickly disappeared from the PBMC culture within 12 hours. Further study of purified the CD14+ monocytes showed that both H7N9 and H5N1 caused rapid down regulation of cell surface CD14 molecules, induced massive activation of caspase 3. TNEUL assay indicated that H7N9 and H5N1 induced apoptotic cell death in monocytes. Overall, these results suggested H7N9 virus is highly infective to human immune cells; infection of PBMCs provoked similar profile of cytokine responses and massive apoptosis of monocytes as seen in highly pathogenic H5N1 virus infection. H7N9 and H5N1 may share similar pathogenic mechanisms to cause severe disease in humans.

Biography:

Zhu Houshun is the PhD student in the department of Medicine of the University of Hong Kong. His research mainly focuses on the treatment of influenza infection.

Abstract:

Mouse beta-Defesin 4(mBD4) is mainly produced by epithelial cells and should play an important role during influenza infection. Firstly, we showed that mBD4 was quickly increased in LA4 cells at 6 hours after inoculation with A(H1N1)09 virus and remained upregulated until 24 hours post infection. The induction of mBD4 was positively correlated with initial virus inoculation doses.The time course for the induction of mBD4 was in parallel with the upregualtion of inflammatory cytokine IL-6 and TNF-α. The expresssion of mBD4 in mouse respiratory tissue was studied and compared between young(6-8 weeks) and aged (72 weeks) mice. IHC staining of formalin fixed mice trachea and lung tissues showed there was stronger expression of mBD4 in epithelial cells lining trachea and broncheoles in aged mice which indicated a higher basal expression of mBD4 in aged mice respiratory tissues. Upon infection with A(H1N1)09 virus, a quick induction of mBD4 in young mice trachea tissue was observed at 12h p.i. and maintained at this level until day 4 p.i.. However, despite the higher basal level, there was no further induction of mBD4 in aged mice trachea tissues. For the lung tissues, delayed induction of mBD4 was observed in aged mice following A(H1N1)09 infection, but no increase was observed in the young mice lung tissues. Accordingly we also see a lower viral load and cytokine levels in young mice. After giving the recombinant mBD4 protein after infection of A(H1N1)09 in aged mice, we saw a reduced viral load in respiratory tissues.

Biography:

Irina Leneva has completed her PhD at the age of 28 years from Research Institute for Viral Preparations ( Moscow, Russia) and postdoctoral studies from Centre of Chemistry of Drugs ( Moscow, Russia). She is the Head of Experimental Virology Laboratory of I.Mechnikov Institute for Vaccines and Sera. Irina Leneva has nearly 50 publications in reviewed journals. She is the virology scientific councilor for the Russian Society for Infection Diseases. Additionally, she is reviewer for several scientific journals in the areas of virology. Her current research focuses on pathogenesis of viral respiratory diseases, mainly , vaccine and antiviral development against biological threat agents and emerging pathogens, clinical trials of antivirals and vaccines, monitoring resistance to antivirals. Irina Leneva is also interested in developing novel assys and animal models for testing new drugs targeting respiratoty viruses.

Abstract:

Pneumonia often occurs secondary to influenza infection and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug umifenovir (Arbidol) is licenced in Russia for treatment and propylaxis of acute respiratory infection including influenza A and B infection.. In the present study, we investigated the efficacy of umifenovir or oseltamivir in a mouse model of secondary S. aureus pneumonia following A/California/04/2009 (H1N1) influenza virus infection. We also performed a clinical study on the effectiveness of umifenovir in reducing flu-associated pneumonia. Experiments in mice showed that oral treatment with oseltamivir (20 mg/kg/day) and umifenovir (40 and 60 mg/kg/day ) improved survival in mice from 0% to 90%, significantly prolonged survival and abolished weight loss. The treatments also inhibited virus titer by ≥2 logs and viable bacterial counts in the lungs of mice. The lungs of mice treated with oseltamivir or umifenovir showed less-severe histopathologic findings compared to the control group. The observation case-control clinical study was set up in season 2010/2011 and 2014/2015 and included 5287 patients admitted to 88 hospitals with acute respiratory viral infections (ARVI) from 50 regions of the Russian Federation. The analysis showed that in high-risk groups of patients the incidence of bacterial complications (pneumonia) was higher than the average for the study population. Our observational studies suggest the benefit of early umifenovir treatment (i.e. within 48 hours after illness onset) in reducing pneumonia incidence in high-risk .

Biography:

Zhanqiu Yang has completed his MD at the age of 35 years from Wuhan University School of Medicine. He is the director of Institute of Medical Virology, Wuhan University. He has published more than 150 papers in reputed journals and has been serving as an editorial board member of repute.          

Abstract:

Jiawei-Yupingfeng-Tang (JYT) is a Chinese herbal formula which is widely used against respiratory tract illness. However, its effect against respiratory virus remains unknown. Influenza virus (IFV) and human respiratory syncytial virus (HRSV) cause million cases of severe illness per year and many of them developing into lethal pneumonia. The aim of this study is to evaluate whether JYT can be used in the treatment of such infections. Methods: The effect of the JYT against IFV and HRSV was tested by plaque reduction assay in the cell lines A549. The expression of ICAM-1 was determined by real-time RT-PCR and Western blot. A lethal influenza infected mice model developing into interstitial pneumonia was used to evaluate the effect of JYT in vivo. Results: JYT extract dose-dependently inhibited both IFV and HRSV when given before, simultaneous and after viral infection. And it was more effective to block the entry of virus. Furthermore, pre-treatment with JYT can reduce the susceptibility of cells to the invasion of HRSV by inhibiting the expression of ICAM-1. Importantly, JYT extract increased the survival rate of lethal influenza-infected mice, prolonged survival time and alleviated the virus-induced lung lesion, which is compatible with that of ribavirin treatment. Conclusion:. These data support JYT as an alternative modality to be used in the treatment of respiratory viral infection induced by HRSV and IFV.

Biography:

Mona Timan Idriss is presently working as a lecture at faculty of pharmacy, department of microbiology, Sudan International University. Her main and current research work on influenza virus. She completed her master research in Japan and she is pursuing  her PhD in Japan and Thailand and Sudan.

Abstract:

We investigated the anti-influenza virus activity of Acacia nilotica and possible mechanism(s) of action in vitro. We found that Acacia nilotica has anti-influenza-virus activity, and both pre-incubation of virus prior to infection and post-exposure of infected cells with Acacia nilotica extract significantly inhibited virus yields. Influenza-virus-induced hemagglutination of chicken red blood cells was inhibited by Acacia extract treatment, suggesting that Acacia can inhibit influenza A virus infection by interacting with the viral hemagglutinin. Furthermore, Acacia extract significantly affect nuclear transport of viral nucleoprotein (NP). To best of our knowledge, this study revealed for the first time that Acacia nilotica extract can inhibit both viral attachment and replication and offers new insights into its underlying mechanisms of antiviral action. The fruit husk ofAcacia nilotica collected from Sudan and Extracted with70% methanol. The crude extract was screened for its cytotoxicity against MDCK cell line by alamar Blue assay and WST-1 assay. Antiviral properties of the plant extract was determined bycytopathic effect inhibition assay and virus yield reduction assay(plaque assay). Time of addition assay, and nuclear export mechanism were also performed. 

Biography:

TBA

Abstract:

The Influenza, the most contagious of the Acute Respiratory Infections, is considered like an emergent and re-emergent illness, due to the wide circulation of old and new variants among the world population. The World Health Organization estimates that influenza accounts for a quarter to half a million deaths worldwide. Vaccination is currently the only practical means of reducing or counteracting this burden of mortality and morbidity in the community. The production of an optimal influenza vaccine requires the continuous global monitoring of influenza by the National Influenza Centre. The Cuban National Influenza Center is located at the Pedro Kouri Institute and has the responsibility to carry out the national virological surveillance of influenza and others respiratory viruses. During the past 10 years, it had been working together with national health authorities on the planning, implementation and improvement of the national surveillance program of Acute Respiratory Infections. From, 2009 to 2014, 38 935 respiratory samples from patient with clinical diagnosis of Acute Respiratory Infection were processed using an algorithm of molecular diagnosis for the detection of 16 respiratory viruses. The total of positive samples to influenza viruses were characterized molecularly; including the nucleic acid sequencing. The mayor positivity was detected for influenza A virus, particularly for the influenza A(H1N1)pdm09, following influenza B viruses. In 2012 we detected the reintroduction of influenza B lineage Yamagata associated with a high rate of morbidity. Most characterized influenza A viruses matched with the vaccine strains with the exception of the circulating viruses during the season 2014-2015. These results suggest a low preventive effect of the seasonal influenza vaccine for the next season. However, the vaccine effectiveness may vary throughout the influenza season. The early estimates of influenza vaccine effectiveness obtained in mid-season may drop during the season. This situation should be kept in mind given its implications for clinical practice and public health. 

Biography:

Taijiao Jiang is a professor of computational and systems biology at Chinese Academy of Medical Sciences & Peking Union Medical College. Dr. Jiang was trained in both biology and computer science, with a Ph.D. of Molecular Biology from Chinese Academy of Sciences (1999) and a Master degree in Computer Science from Yale University (2003). He has been working on computational and systems biology since 1999 including the postdoctoral work with Professor Sidney Altman of Yale during 1999-2001 and with Professor Amy Keating at MIT during 2003-2005. In 2005, Dr. Jiang joined in the Institute of Biophysics, Chinese Academy of Sciences. Since 2013, Dr. Jiang, as one of the co-founders, has participated in setting up the Suzhou Institute of Systems Medicine (ISM), a joint initiative between Chinese Academy of Medical Sciences and the local government of Suzhou Industry Park (SIP) and Suzhou Municipality.

Abstract:

The advancement of high throughput sequencing technology coupled with internet technology has enabled us to acquire massive genomic data for in-depth understanding of disease mechanisms, facilitating more effective strategies for disease prevention and treatment. In our lab, by focusing influenza viruses, we have developed a series of methods to model influenza antigenic evolution from the massive gene data collected during influenza surveillance carried out by Chinese Center for Disease Control and Prevention (China CDC). Furthermore, we have proposed network-based approaches for effective seasonal influenza vaccine strain selection. No doubt, the effective mining of the big genomic data related to diseases will not only greatly facilitate the prevention and control of infectious diseases but also advance the precision medicine for complex diseases like malignant tumors.