Day 1 :
Keynote Forum
Hiroshi Kida
Hokkaido University Research Center for Zoonosis Control, Japan
Keynote: For the control of avian and human influenza
Time : 09:30-10:00
Biography:
Hiroshi Kida, DVM, PhD, Member of the Japan Academy, is Professor Emeritus, Head of the Research Center for Zoonosis Control at Hokkaido University, Sapporo, Japan, Head of the OIE Reference Laboratory for Avian Influenza, and Head of the WHO Collaborating Centre for Zoonoses Control. He has experiences of the development of influenza and leptospirosis vaccines as Research Officer at Takeda Chemical Industries, Ltd (1969-1976). Since 1976, he has devoted himself to research and education at Hokkaido University and been the recipient of several awards and honors such as Japan Academy Prize for “Studies on Control of Influenza -Mechanism of Emergence of Pandemic Influenza Virus Strains in Poultry, Domestic Animals and Humans, and Molecular Basis of the Neutralization of Viral Infectivity with Antibodies”. He is the author of 304 original articles and 142 book chapters and reviews.
Abstract:
H5 highly pathogenic avian influenza viruses (HPAIVs) have spread around Eurasia and Africa. Unless these viruses are eradicated from poultry in Asia, those may perpetuate in the lakes where migratory water birds nest in summer in Siberia and outbreaks of HPAI must occur everywhere in Eurasia every year. We thus strongly propose to eradicate those HPAIVs from Asia by stamping-out without misuse of vaccine through international collaboration.\r\n Each of the past 4 pandemic influenza viruses is thought to be a reassortant generated in a pig between avian influenza virus and the preceding human strain. We have shown that pigs are susceptible to infection with both of avian and mammalian influenza viruses of different HA subtypes, generating reassortants with human receptor specificity. Since each of influenza A viruses of all known subtypes perpetuates among migratory ducks and their nesting lake water and avian viruses of any subtype can contribute genes in the generation of reassortants in pigs, none of viruses 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 2,000 low pathogenic avian influenza virus strains of 144 combinations of 16 HA and 9 NA subtypes for vaccine strain candidates and diagnostic use (http://virusdb.czc.hokudai.ac.Jp/vdbportal/view/index.jsp).\r\n In addition, it is strongly proposed that surveillance of swine influenza and drastic improvement of seasonal influenza vaccine are of crucial importance in order to assure the effective preparedness for pandemic influenza.\r\n
Keynote Forum
Bing Sun
Chinese Academy of Sciences
China
Keynote: Both PB1 473V mutation in RNA polymerase activity and NP sumoylation play an important role in the pathogenesis of influenza virus infection
Time : 10:00-10:30
Biography:
Bing Sun joined Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China and was a Chief of Lab of Molecular Immunology. He has been appointed as Co-Director and Head, Lab of Molecular Virology in Institute Pasteur of Shanghai, Chinese Academy of Sciences, China. He has been working on dendritic cell maturation and Th1/Th2 cell differentiation over twenty years. He has been working on viral ion channel protein; he has discovered 3a protein of SARS and P7 protein of HCV are an ion channel protein, which are important for viral life cycle and potential a drug target. He has been working on RNA polymerase in influenza A virus.
Abstract:
Influenza A virus is a substantial threat to human health. After 1997, the emergence of highly pathogenic H5N1 avian viruses in humans caused great concern about the possibility of a new pandemic. It is reported that PB2 627K plays an important role in the cross-species transmission of avian viruses. In the new emergence of H7N9 avian viruses, we found the PB2 E627K promoted the replication and pathogenicity in mice. However, some avian viruses carrying PB2 627E still can replicate well in mammalian cells and animals. That means there are some key points can compensate the loss function of PB2 627E. By the mini-replicon system, we identified that PB1 473V and 598P can compensate the polymerase activity of avian viruses carrying 627E in mammalian cells and can restore the pathogenicity of viruses in mice. During the life cycle, viruses take advantage of host post-translational modifications for their own benefit. It was recently reported that influenza A virus proteins interact extensively with the host sumoylation system. Thereby, several viral proteins, including NS1 we had reported, are sumoylated to facilitate viral replication. However, the sumoylation in other proteins of influenza A virus is not fully understood. In our study, we found that influenza A virus nucleoprotein (NP) is a target of sumoylation in both NP-transfected cells and virus-infected cells at the two most N-terminal residues, lysine 4 and lysine 7, and that the sumoylation at lysine 7 of NP is highly conserved across different influenza A subtypes and strains. The NP-sumoylation-defective virus, WSN-NPK4,7R virus, exhibited an early cytoplasmic localization of NP. The growth of the WSN-NPK4,7R virus was highly attenuated compared to that of WSN-WT virus. We evaluated whether members of the PIAS family, the best-characterized E3 ligases, could function as an E3 ligase for NP. Among all PIAS homologs, over-expression of PIASxa had the strongest effect on NP sumoylation, suggesting that PIASxa is the predominant E3 ligase for NP. Thus, sumoylation of influenza A virus NP is essential for intracellular trafficking of NP and for virus growth, illustrating sumoylation as a crucial strategy extensively exploited by influenza A virus for survival in the host.
Keynote Forum
Beatrice Nal
Brunel University London
UK
Keynote: Interactions between viral structural proteins and human host factors
Time : 10:45-11:45
Biography:
Dr Beatrice Nal graduated with a PhD in Immunology in 2002 (CIML, France). After a post-doc at Institut Pasteur in Paris she joined the Hong Kong University-Pasteur Research Centre and was appointed Research Assistant Professor and head of the Virus-Host Interactions group in 2006. She transfered her lab to Brunel University London in 2011. Her major research interest is the understanding of molecular determinants of viral pathogenesis. She has made new important discoveries on mechanisms of virus assembly and viral cellular interactomes for dengue virus, coronaviruses and influenza A virus.
Abstract:
Elucidation of networks of interactions between viruses and host cells will pave the way towards the understanding of molecular determinants of cytopathogenicity and ultimately the design of novel therapeutics. Our strategy is to identify human restricting and enhancing factors of viral infections. We focus on viral structural proteins, which not only play key roles at early and late stages of the replication cycle but also act as regulators of cellular processes through specific interactions with cellular pathways. We have conducted a series of yeast two-hybrid screens using the cytosolic domains of the structural proteins of human coronavirus and influenza A virus as baits. Our studies have revealed novel interactions that have opened new routes of investigation. We have identified a PDZ-binding motif in the C-terminal domain of the SARS-CoV small envelope protein, responsible for interaction and mislocation of the PDZ domain-containing tight junction protein PALS1, loss of epithelial cell polarity and potentially enhancement of viral dissemination. We found that the interaction between SARS-CoV Spike C-terminal tail and the cytoskeleton-binding protein ezrin is involved in restriction of viral entry and limits Spike-dependent fusion. We have identified that the C-terminal domain of influenza A virus M2 interacts with human annexin A6. We found that annexin A6 expression alters influenza A virus morphogenesis and restricts release of progeny virions.
- Track 1-Molecular virology and immunology
Track 2: Virus host interaction/pathogenesis/transmission
Track 8: Implications and Ethical preparedness for pandemic influenza
Chair
Hiroshi Kida
Hokkaido University, Japan
Co-Chair
Bing Sun
Chinese Academy of Sciences, China
Session Introduction
Karin E. Peuschel
Meissenberg Clinic Inc.
Switzerland
Title: An immunomodulating treatment strategy of influenza with propranolol, a non-selective lipophilic beta-blocker
Time : 11:45-12:10
Biography:
Dr. Peuschel has studied medicine and molecular biology at the University of Zurich, as well as psychiatry and psychotherapy at the University of Lausanne. She has completed her MD from the University of Zurich, has worked in research in molecular biology at the University of Zurich and has obtained federal diplomas in general medicine as well as in psychiatry and psychotherapy. She is currently head of department at the Meissenberg Clinic in Zug, Switzerland. She has published 7 papers indexed in PubMed, she has been presenting her work at various conferences, and has been invited to conferences in Europe, the US, China, Japan, Thailand, India and the United Arab Emirates.
Abstract:
Clinical observations suggesting an antiviral effect of propranolol have been confirmed at an observational level for influenza infections, as well as for other viral infections like herpes simplex I and herpes zoster virus infections. A theory of the mechanism of this antiviral effect has been developed, and examples of published observations apparently confirming the antiviral effect of propranolol have been analyzed based on the assumed mechanism. The proposed mechanism is an increased activity of most cells of the immune system via an activation of the cAMP-PKA pathway, reducing the inhibitory impact of some stress-related influences on the immune system. In contrast, in tissues activated by stress the cAMP-PKA pathway is activated by beta-receptor agonists. A larger view concerning the impact of stress on tissues inactivated versus tissues activated by stress is proposed and the potential consequences concerning treatment strategies are presented.
Ai Ikejiri
Tokyo Metropolitan Institute of Medical Science
Japan
Title: Highly pathogenic avian influenza virus (H5N1) causes severe symptoms due to insufficient induction of humoral immune responses
Time : 12:10-12:35
Biography:
Ai Ikejiri has completed her PhD from Keio University School of Medicine (Tokyo, Japan) and joined National Institute of Infectious Diseases. Since 2014 she is a researcher of Tokyo Metropolitan Institute of Medical Science. She is interested in the implication of the host immune responses in influenza pathogenicity.
Abstract:
It has been reported that fatal outcome of the patients infected with highly pathogenic avian influenza (HPAI) virus (H5N1) is associated with high viral load. However, the reason why patients cannot eliminate the viruses and succumb to them is not well known. To clarify the immune responses against H5N1 HPAI virus, we investigated temporal changes of the humoral immune response in animal models infected with low pathogenic pandemic H1N1 or H5N1 HPAI viruses. BALB/c mice were infected intranasally with A/Tokyo/2619/2009 (H1N1) or A/Whooper swan/Hokkaido/1/08 (H5N1). Cynomolgus monkeys were infected with H1N1 or H5N1 viruses via oral, nasal, and tracheal routes. Mice infected with H5N1 virus exhibited significant weight loss and nearly 100% mortality. In contrast, mice infected with H1N1 survived without weight loss. The titers of neutralizing and binding antibody against H5N1 virus-infected mice were significantly lower than those of H1N1 virus-infected mice. The H5N1 virus infection induced thinner outer layers of B-cell follicles. Similarly, cynomolgus monkeys could not induce antibodies against H5N1 virus, resulted in marked weight loss and manifestation of diffuse severe pneumonia. The similar alteration in formation of B-cell follicles was also observed in the monkey model. On the other hand, H1N1 virus-infected monkeys could induce successfully virus binding and neutralizing antibodies and exhibited only partial inflammatory foci. These results imply that the severe symptoms in H5N1 virus infection were associated with insufficient activation of B-cells to induce efficient neutralizing antibodies.
Remigiusz Worch
Institute of Physics
Polish Academy of Sciences
Poland
Title: Biophysical studies of Influenza virus proteins involved in membrane fusion and host RNA cleavage
Time : 12:35-13:00
Biography:
Remigiusz Worch has completed his PhD at the University of Warsaw in 2007 and postdoctoral studies at the Biotechnology Center of the Technical University Dresden, Germany (BIOTEC) as the Alexander von Humboldt fellow. Currently he is an assistant professor at the Biological Physics Group, Institute of Physics, Polish Academy of Sciences in Warsaw, Poland.
Abstract:
Membrane fusion induced by hemagglutinin fragment, the so-called fusion peptide (HAfp), and host RNA cleavage by viral polymerase are the key steps of influenza replication. A 20-amino acid HAfp1-20 peptide has a boomerang-like shape, however it has been shown recently that extending HAfp1-20 by three more conservative residues (to HAfp1-23) leads to a helical hairpin formation. We determined partition coefficients Kx for a series of peptides in their native forms using tryptophan fluorescence. HAfp1-23 showed more favorable interaction than HAfp1-20 with DOPC at pH 7.4, but at endosomal pH 5.0 the difference was negligible. Both peptides lead to liposome content leakage in a similar fashion, as measured in single giant unilamellar vesicles (GUV) using fluorescence microscopy. Nevertheless HAfp1-23 had larger liposome fusion capacity, as concluded from FRET experiments and showed a distinct lipid bilayer distortion by fluorescence lifetime imaging. Despite intensive studies on endonucleolitic polymerase domain (PA-Nter), the existing results on divalent ion preference are contradictory. We quantified the PA-Nter cleavage reaction rates by fluorescence cross-correlation spectroscopy (FCCS). This microscopic technique provides rapid, highly sensitive and real-time monitoring of single molecule interactions. In the regime of enzyme excess, using ss-DNA at nanomolar concentrations, we determined the maximum reaction rates at 0.51 and 0.77 nM/min for Mg2+ and Mn2+, respectively. Our results show the superiority of FCCS technique for real-time kinetic analysis over the electrophoretic assays. Presented studies constitute a step towards better understanding of fusion and RNA cleavage mechanisms. Supported by Scientific Polpharma Foundation, 2012/07/D/NZ1/04255 and Foundation for Polish Science grants.
Ke Xu
Lab of Molecular Virology
Institut Pasteur of Shanghai
Chinese Academy of Sciences
China
Title: Mechanism and functional studies on sumoylation of influenza A virus nucleoprotein
Biography:
Ke Xu has completed her PhD at the age of 27 years from Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, and joined Institut Pasteur of Shanghai as an assistant and then associate Principal Investigator. Her research Interests are virus-host interactions of influenza A virus, specially post-translational modifications of viral proteins. She has published 20 papers in reputed virology journals. Her recent work of FluA NP sumoylation was published Journal of Virology as Spotlight paper where she contributed as the corresponding author. She has also serving as an editorial board member of reputed journal, Archive of Virology.
Abstract:
To establish efficient infection in host cells, viruses rely on cell machinery for its own benefit. One example of a key cellular signaling targeted by viruses is host post-translational modifications. Recently, it has been reported that influenza A virus proteins interact extensively with host sumoylation systems, and several viral proteins, such as NS1, M1, and NP are sumoylated to facilitate virus growth. In our recent work, by screening viral proteins that constitute influenza A virus viral ribonucleoproteins (vRNP), we found nucleoprotein (NP) to be a bona fide target of sumoylation in both transfected and infected cells. We further identified the sumoylation sites of NP locate at the very N-terminal lysines, which is highly conserved among different influenza A subtypes and strains including the newly discovered human H7N9 virus. Interestingly, a caspase-cleavaged NP with 1-16aa deletion was not sumoylated by losing the N-terminal lysines. Functionally, sumoylation of NP does not affect the polymerase activity but regulate the transport dynamics of NP. As a consequence, the NP sumoylation-defective virus is highly attenuated as compared to WT virus. Morphologically, the NP sumoylation-defective viruses form filamentous particles, while WT viruses exhibit spherical phenotype. Besides, we found that knocking down Ubc9 decreases viral sumoylation and attenuates virus growth, while over-expression of PIASxa enhances NP sumoylation as well as virus growth. These data indicate that sumoylation of viral proteins, especially NP protein is essential for virus production in infected cells and plays an important role in determining the virus morphology.
Kin-Chow Chang
School of Veterinary Medicine and Science, University of Nottingham, UK
Title: Bat lung epithelial cells show variable species-specific resistance to human and avian influenza viruses
Time : 14:00-14:25
Biography:
Kin-Chow Chang is Professor of Veterinary Molecular Medicine at the University of Nottingham.His key research focus is on mammalian host innate resistance to pathogenic influenza virus infection.One strategic approach adopted is to compare host response to virulent influenza virus infection (such as avian H5N1 virus) between resistant (e.g. pig, duck and bat) and susceptible (human and chicken) host species to identify targets for the development of intervention therapy to reduce disease severity.
Abstract:
Bats (order Chiroptera) are natural reservoirs for zoonotic viruses that cause some of the deadliest diseases in humans, including filoviruses (such as Ebola and Marburg viruses), lyssaviruses, severe acute respiratory syndrome (SARS)-related coronaviruses and henipaviruses (e.g. Hendra and Nipah viruses). Recently, two novel influenza viruses, H17N10 and H18N11, were also identified in bats through deep sequencing analyses (1). Despite being hosts to such an array of pathogens, bats generally show no or mild clinical symptoms to their presence, a phenomenon that is largely a mystery and a potential medical treasure trove that offers new insights into dealing with such pathogens in humans and affected animals. The lack of illness does not mean that bat cells are not infected by such viruses. Bat cells are susceptible to virus infections such as paramyxoviruses, filoviruses and influenza viruses (2), and show varying degree of permissiveness/resistance to virus replication, a pre-requisite for the hosts to acquire carrier status. Murine encephalomyocarditis virus causes severe cytopathic damage to bat lung epithelial cells (TB1 Lu) of Tadarida brasiliensis, and Ebola virus shows persistent infection in such cells (3). TB1 Lu cells also display resistance to reovirus infection; infected cells show no cytopathic effects and rapid decline in virus production, however, low virus release is maintained for at least 2 months (3). Insights into bat immune resistance could lead to novel therapeutic developments targeting such viruses. Although bats are not known to act as natural hosts for human and avian influenza viruses, chimeric virus housing the 6 core genes from bat H17N10 replicates well in human primary airway epithelial cells and mice, but poorly in avian cells and chicken embryos without further adaptation (4). Furthermore, viral ribonucleopolymerase complex (vRNP) from bat H17N10 virus is able to drive with high efficiency the non-coding region of human H1N1 virus (A/WSN/1933) in vRNP minigenome reporter assays, suggesting the potential for viable reassortment between bat and conventional influenza A viruses in non-bat hosts (5). Likewise, bat TB1 Lu cells appear to be more resistant than other bat cells to avian (H7N7 and H9N2) and porcine (H1N1) influenza viruses based on the extent of viral nucleoprotein (NP) detection at 24h of infection (2). Additionally, infected bat (Pteroptus alecto) kidney cells show virus reassortment between human H1N1 virus (A/WSN/1933) and highly pathogenic avian influenza (HPAI) H5N1 virus (A/Vietnam/1203/04) (6). We hypothesise that bat cells possess novel innate immune ability to resist conventional influenza virus infection. To this end, we aim to examine the innate response of lung epithelial cells of T. brasiliensis (a medium insectivorous bat), Eidolon helvum (a large fruit bat) and Carollia perspicillata (a small fruit and insect eating bat) to influenza A virus infection to understand how the virus is inhibited by the host. We found clear evidence of host innate resistance to permissive virus replication in epithelial cells of the three bat species which appears to be independent of type I and III interferons. There were, however, clear differences between bat species in the distribution of sialic acid virus receptors, and in relative resistance to avian and human influenza viruses.
Ana Carolina Arcanjo
Universidade de BrasÃlia, Brazil
Title: Human genetic variability and susceptibility to severe influenza infection
Time : 14:25-14:50
Biography:
Ana Carolina Arcanjo is a scientist who received her MSc in 2012 in Animal Biology at the University of Brasilia, Brazil and is currently PhD student at the same institution. Her major area of study is human population genetics and evolution.
Abstract:
Influenza infection has been a research topic for over 70 years. Although some aspects of the immunological response to influenza are known, there is still debate on how the host genetic variability affects its prognosis. This work explores genomic variability in host genes mediating host-pathogen interactions. A genomic approach was implemented, focused on major gene variants in the 1000 Genomes Project, aimed at describing the variability across human populations. As an example, the allelic frequency of a SNP located in the CD55 gene promoter, which has previously been directly implicated in the prognosis of influenza infections. The rs2564978 T/T genotype, highly associated with severe form of influenza, is more frequent in the Chinese (54% in CHB, and 63% in SAN), while in others it ranged from 1.7% (Yoruba) to 39% (Japanese). The Southern Asians were the most affected, with documented deaths ranging from 3.3-4.4 deaths/100000 inhabitants. The rs2564978C/C, associated with a less severe form of influenza, is more frequent in Europeans and Western Pacific, where the protective C allele frequency ranges from 70-90%. These populations showed the smallest rates of deaths (1.8 and 1.7/100000 inhabitants, respectively). Evolution of host–pathogen interactions yields variants in host genes, several of which are associated with bad or good infection prognosis. These variants have been shown to be polymorphic in different human populations, which could be further correlated with the different rates of morbidity/mortality to influenza-A. Therefore, the susceptibility to severe influenza in humans is, at least to some extent, heritable.
Zhou Jie Jane
The University of Hong Kong, China
Title: Identification of TMPRSS2 as a susceptibility gene for severe 2009 pandemic A (H1N1) influenza and A (H7N9) influenza
Time : 14:50-15:15
Biography:
Zhou Jie Jane is the Research Assistant Professor from the Department of Microbiology at the University of Hong Kong. Her major research interests include host genetics of infectious diseases, pathogenesis of respiratory viral infection. She has published papers in reputed journals.
Abstract:
The genetic predisposition to severe A (H1N1) pdm09 influenza was evaluated in 409 patients including 162 severe cases and 247 mild controls. We prioritized candidate variants based on the result of a pilot GWAS and a lung eQTL dataset. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (OR 2.11, 95% CI 1.18~3.77, p=0.0113) to severe A (H1N1) pdm09 influenza. A potentially functional SNP, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A (H7N9) influenza in 102 A (H7N9) patients and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A (H1N1) pdm09 influenza. The same variants also increase the susceptibility to human A (H7N9) influenza.
Wei Wang
Center for Biologics Evaluation and Research
US-FDA
USA
Title: Intermonomer interactions in hemagglutinin subunits HA1 and HA2 affecting hemagglutinin stability and influenza virus infectivity
Time : 15:15-15:40
Biography:
Wei Wang obtained his PhD from University of Saskatchewan and completed Post-doctoral trainings from National Cancer Institute and US Food and Drug Administration. He is a reviewer and research scientist at Center for Biologics Evaluation and Research, US Food and Drug Administration.
Abstract:
Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop) to helix transition, which releases the fusion peptide at the HA2 N-terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable relative to other seasonal influenza strains. We found that residue 205 in HA1 and 399 in the B loop of HA2 (residue 72, HA2 number) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity.
- Symposium: "Control of avian influenza and preparedness for pandemic influenza"
Location: Madison
Chair
Hiroshi Kida
Hokkaido University, Japan
Session Introduction
Robert G Webster
St. Jude Children's Research Hospital Memphis, USA
Title: The impact of influenza virus ecology on pandemic preparedness
Biography:
Robert G Webster received his BSc and MSc in Microbiology from Otago University in New Zealand. In 1962, he earned his PhD from the Australian National University and spent the next two years as a Fullbright Scholar working on influenza in the Department of Epidemiology at the University of Michigan, Ann Arbor. He is the Rose Marie Thomas Chair of the Virology Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Director, WHO Collaborating Center on the Ecology of Influenza Viruses in Lower Animals and Birds. He is Professor in the Division of Virology, Department of Infectious Diseases at St. Jude Children's Research Hospital, and Director of the World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds. His interests include the emergence and control of influenza viruses, viral immunology, the structure and function of influenza virus proteins, and the development of new vaccines and antivirals. The major focus of his research is the importance of influenza viruses in wild aquatic birds as a major reservoir of influenza viruses and their role in the evolution of new pandemic strains for human and lower animals. His curriculum vitae comprise over 480 original articles and reviews on influenza viruses. He has trained many scientists who now contribute to our understanding of the evolution and pathogenesis of influenza.
Abstract:
It is now recognized that the global reservoirs of influenza A viruses are in the aquatic birds and bats. For many years there was reluctance to accept the relevance of influenza viruses in natural reservoirs as the source of genes for influenza viruses that are of relevance to veterinary and human public health. Since the early 1990s, there have been multiple events, including emergence of highly pathogenic H5N1 and low pathogenic H7N9, the emergence of pandemic 2009 H1N1 influenza viruses in humans and the detection of multiple reassortants in swine and more recently the detection of multiple different reassortants of the H5 clade of influenza viruses in domestic poultry. These events leave no doubt about the relevance of the influenza gene pool in natural reservoirs. The rapid intercontinental transmission of clade 2.3.4.4 H5 influenza viruses raises the question of whether there has been a paradigm shift in the ecology of influenza viruses in wild waterfowl. The available evidence suggested that highly pathogenic influenza viruses were not perpetuated in wild aquatic birds. Has this changed? Long term surveillance of influenza viruses in wild aquatic birds in Alberta, Canada and Delaware Bay, United States showed peaks of H7N3 activity in wild birds before the emergence of highly pathogenic H7N3 viruses in Chile, Canada and Mexico. Genomic studies of the H1N1 influenza viruses from aquatic birds at Delaware Bay suggest that the H1N1 influenza viruses from shorebirds may have the unique property of ferret to ferret aerosol transmissibility. The importance of influenza viruses from natural reservoirs in pandemic preparedness is still grossly under-appreciated. Genomic analysis of the influenza viruses in natural reservoirs is needed for future pandemic preparedness.
David Charles Jackson
The University of Melbourne, Australia
Title: How to stop influenza and its sequelae
Biography:
David Jackson has been an active researcher in immunology and immunochemistry over the last 40 years. His research efforts are now focused on the design, assembly and evaluation of innovative vaccines which have led to pre-clinical and clinical evaluation of vaccine candidates for influenza, hepatitis C virus, Group A streptococcus, Mycobacterium tuberculosis and human papilloma virus. He has also developed candidate vaccines against methamphetamine and cocaine and against the reproductive hormone luteinizing hormone releasing hormone. He has trained more than 50 graduate, postgraduate, doctoral and postdoctoral scholars and published more than 200 original research papers, invited reviews and book chapters in immunology, chemistry, biochemistry and vaccinology. He was one of the founders of the Cooperative Research Centre for Vaccine Technology and is senior inventor of a number of patents with licenses issued to the pharmaceutical industry. One of his inventions resulted in a first-in-man clinical trial of a synthetic epitope-based vaccine against hepatitis C virus. He is co-founder of 2 start-up biotechnology companies both of which are based on his own inventions. In the last five years his work has attracted more than twenty million dollars in research grants from nationally and internationally competitive sources, industry and investors. He is a Senior Principal Research Fellow with the National Health & Medical Research Council of Australia, a Professor in The University of Melbourne and a Chief Investigator of an NH&MRC Program Grant. In 2014 he was appointed Distinguished Professor in Hokkaido University, Japan.
Abstract:
Promising new approaches to combat infectious disease involve modulation of the host’s innate immune system using agents which stimulate appropriate responses against a pathogen. Because these agents directly target the host rather than the pathogen, they are unlikely to result in the development of anti-microbial resistance even after repeated use. With the development of anti-microbial resistance to antibiotics and the need to update vaccines to accommodate pathogen evolution, the development of alternative forms of prophylactic agents with a broader spectrum of activity has emerged as an unmet medical need. The rapid response time and broad nature of the innate immune system indicates that treatment with these agents will provide a broader spectrum of protection and could be used in combination with other anti-microbial agents including vaccines. This presentation will demonstrate the potential of Pam2Cys as an agent that can stimulate the innate immune system to provide short term but immediate and antigen-independent protection against infection with respiratory pathogens and also provide a means of simultaneously delivering a vaccine to provide long term, antigen-specific immunity.
Biography:
Lorena Brown is a Professor at the University of Melbourne and at Hokkaido University. She is a Lecturer in Virology to students of Science and Medicine and also heads a laboratory dedicated to understanding and controlling influenza. Her work is focused on researching and evaluating new vaccines designed to combat both seasonal and highly lethal avian strains of influenza, including vaccines that induce cross-reactive T cell responses. Along with a combined expertise in immunology and basic virology, her teamed is skilled in molecular virology techniques, which are used to understand the detailed replication of influenza virus and disease pathogenesis.
Abstract:
Vaccines that exert their effects solely through the induction of highly specific neutralising antibodies can be effective but their benefit diminishes in a scenario of vaccine mismatch or if a new subtype of virus emerges. Cross-protective responses, such as those invoked and continuously boosted by natural infection, probably account for why most individuals experience clinical influenza on only a few occasions during their lifetime in response to antigenically drifted influenza strains. Cross-reactive immunity may also provide some protection against severe illness following infection with virus of a novel subtype. Current split virus vaccines induce very little if any cross-protective immunity against heterologous subtypes of virus and vaccine strategies that enable such responses would represent a substantial improvement. Proof of principle studies using two different strategies that potentially induce both highly specific neutralising antibody and heterosubtypic immunity in the form of cross-reactive cytotoxic T cells will be reported. The first of these is delivery of live virus by a non-productive route and the second is delivery of split virus vaccine in combination with an epitope-based TLR2-containing component. The “dose-sparing” effects of such vaccines will be discussed as well as the influence of routes of inoculation on the balance of antibody versus cytotoxic T cell immunity and the potency of the viral clearing response.
Ian Brown
Animal and Plant Health Agency-Weybridge, UK
Title: New and re-emerging challenges for the detection and control of zoonotic animal influenza
Biography:
Ian Brown is the Director of EU/FAO/OIE Reference Laboratory for Avian & Swine Influenza, Animal and Plant Health Agency-Weybridge, United Kingdom and also the Visiting Professor in Avian Virology, University of Nottingham.
Abstract:
Global activity with animal influenza is dominated by persistence, spread, and re-emergence of H5 HPAI. Furthermore this group of viruses have undergone significant antigenetic evolution in recent years. These viruses have remained endemic in several regions whilst in others sustained eradication has been possible. A variety of control methods have been used with an increasing number of countries using vaccination as a single or multiple component where stamping out alone has not proved practical. Multiple clades of H5 HPAI continue to co-circulate and evolve in poultry populations and a several specific groups have been associated with continued zoonotic infection including a rise in cases in Egypt. In the last twelve months there have been developments on a global scale not previously seen. H5N1 virus has re-emerged in central Asia, West Africa and Eastern Europe. However, by far the greatest development of global significance has been the emergence of clade 2.3.4.4 viruses which have spread globally within Asia, Europe and for the first time in North America. To date these viruses appear to be of lower risk for humans but continue to evolve. All these events have revealed significant virus reassortment within the H5 HPAI Eurasian family. Incursion is postulated to have occurred initially via infected migratory waterfowl but the spread and transmission within poultry has most likely occurred through multiple pathways. This presents significant new challenges for the future since the basis for prevention of HPAI infection is through strong biosecurity. Other AI viruses continue to emerge and circulate including LPAI viruses; H7N9 of avian origin in China primarily in human’s since 2013 is noteworthy. Influenza A viruses from pigs are still occasionally associated with human infection most notably H3N2v in North America. A greater understanding of reverse zoonoses reveals these events to pigs occur on a frequent basis.