Day 20 :
- 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.
- Track 3-Antiviral drug development and treatment strategies, including vaccination, Track 9- Strategies for Developing New Antiviral Flu Drugs, Track 12- Vaccines: current and novel approaches
Session Introduction
Masayuki Noguchi
Hokkaido University, Japan
Title: Inhibition of Akt kinase activity suppresses entry and replication of influenza virus
Time : 11:15-11:40
Biography:
Prof. Masayuki Noguchi has completed his PhD in the year 1999 from Jikei University of Medicine. He is the Professor in Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. He was the member of American Society of Microbiology in the year 2000 and also editorial board member for Journal of Bio Chemistry. He has published more than 70 papers in reputed journals.
Abstract:
The possibility of the pandemic spread of influenza viruses highlights the need for an effective cure for this life-threatening disease. Influenza A virus, belonging to a family of orthomyxoviruses, is a negative-strand RNA virus which encodes 11 viral proteins. A numbers of intracellular signaling pathways in the host cells interact with influenza, the viral proteins, which affect various stages of viral infection and replication. In this study, we investigated how inhibition of Akt kinase activity impacts on influenza virus infection by using “Akt-in”, a peptide Akt inhibitor. In PR8 influenza-infected A549 cells, Akt interacted with the NS1 (Non-structural protein1), and hence increased phosphorylation of Akt kinase activity and NS1. Treatment of cells with either “TCL1- or TCL1b-based Akt-in” efficiently suppressed Akt kinase activity while decreasing the levels of phosphorylated NS1; this, in turn, inhibited viral replication in a dose- and time-dependent manner. The inhibitory effect on viral replication appears to not be due to inhibition of the production of inflammatory cytokines, including IL-6 and IL-8, in the host cells. Inhibition of Akt kinase activity in the host cells inhibited the efficiency of viral entry, which is associated with decreased levels of phosphorylated glycogen synthase kinase 3, a substrate of Akt. Further, Akt-in treatment of the host cells, which inhibited Akt kinase activity, modestly enhanced induction of autophagy. Taken together, inhibition of Akt kinase activity in host cells may have therapeutic advantages for influenza virus infection by inhibiting viral entry and replication.
Anthony S. Gilbert
hVIVO, UK
Title: ‘The Human Viral Challenge Model – Accelerating Antiviral and Vaccine Development’
Time : 11:40-12:05
Biography:
Dr Gilbert lends a unique blend of medical expertise, both from his clinical experience in the UK’s National Health Service and from his clinical research background. His professional activities have included work in infectious diseases, vaccine development and antiviral research. His virology research includes work in Influenza, RSV and HRV. Having led numerous studies in London's teaching hospitals to International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines, Dr Gilbert brings a wealth of clinical research experience to Retroscreen Virology. For over a decade, Dr Gilbert has played an important role in the development of the Human Viral Challenge Model at Retroscreen Virology. As a Principal Investigator, Dr Gilbert 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. The research has been published in several medical and scientific journals, including ‘Nature Medicine’. Dr Gilbert obtained his Bachelor of Medicine and Bachelor of Surgery degree from the University of the Witwatersrand, Johannesburg. He is a member of the Institute of Clinical Research. He has served as an expert member and Alternate Vice Chair of a National Research Ethics Service (NRES) committee, having been appointed by the Health Research Authority in the United Kingdom.
Abstract:
For over a decade, Human Viral Challenge Studies have successfully been conducted at Retroscreen Virology to develop a series of well-characterised virus stocks, whilst demonstrating that the Human Viral Challenge Model (VCM) 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 VCM also enables fundamental research into the human response to infection and crucial research into modes of infection and transmission between individuals in the community. 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. As Retroscreen Virology has grown and developed, the VCM has become widely accepted as an alternative to traditional early stage field trials to show the efficacy of antiviral or vaccine therapeutics in Influenza, RSV and HRV.
Takahiro Haruyama
Nagasaki University, Japan
Title: Effective defense activity of Honey against influenza virus infection: The combination with neuramidase inhibitors.
Time : 12:05-12:30
Biography:
Takahiro Haruyama has completed his PhD at the age of 38 years from Tsukuba University and studies as assistant professor in Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University. He has published more than 10 papers in international journals.
Abstract:
To control influenza virus infections are one of urgent global issues. In the replication of influenza viruses, the mutants are frequency generated because of the high mutation rate of its RNA dependent RNA polymerase. Even if effective therapeutic agents have been developed, drug-resistant viruses easily emerge and spread all over the world in the blink of an eye. Actually, a large number of resistant viruses against neuraminidase (NA) inhibitors had already been isolated from clinical specimens. In order to respond to the current situation, continuous development of the new antiviral drugs is required. We constructed an in vitro cell-based screening system for anti-influenza virus activities and detected potent anti-influenza virus infection in natural products. We found potent anti-influenza virus activities in “Honey”, and it was suggested that the active components in honey is methylglyoxal (MGO). The mechanism of Honey and MGO against influenza virus was virucidal. Thus we tested the combination activity of Honey or MGO with NA inhibitors. It was confirmed that Honey or MGO synergistically inhibit Influenza replication thus in the presence of low concentration of Honey or MGO IC50 of NA inhibitors lowered up to 1/100 of NA inhibitors alone. However, our results revealed that honey has potent inhibitory activities against influenza virus infection, demonstrating a potential medicinal value as a good partner for current NA inhibitors. Combination of multiple drugs for inhibition of Influenza virus replication could be effective as HAART treatment in AIDS.
Bao-Zhong Wang
Emory University School of Medicine, USA
Title: Novel coated nanoclusters from structure-stabilized influenza H7N9 HA induce enhanced protective immunity
Time : 12:30-12:55
Biography:
Bao-Zhong Wang has completed his PhD in the year of 2003 from Shanghai Institute of Biochemistry, Chinese Academy of Sciences, Shanghai, China. He is an Assistant Professor in the Department of Microbiology and Immunology, Emory University School of Medicine. He has published more than 35 peer viewed papers.
Abstract:
Nanoparticles from antigenic proteins are highly immunogenic because of the novel quality brought from their particulate structures. We developed a two-step procedure to generate protein nanoparticles (nanoclusters) from recombinant trimeric structure-stabilized H7N9 HA (stHA). These nanoclusters have an average diameter of 273.6 nm with a similar Zeta potential to the soluble protein, demonstrating the their comparable solution stability. In a dendritic cell culture, these nanoclusters were reactive to upregulate the CD86 expression and stimulate the production of TNF-α. To evaluate the immunogenicity of the nanoclusters, mice were immunized with either intramuscular (i.m.) or intranasal (i.n.) route. We found that these nanoclusters induced extremely high levels of serum IgG with high neutralization activity as well by i.m route. One i.m. immunization with 10µg of the nanoclusters provided complete protection against a 10 LD50 live H7N9 virus challenge with slight bodyweight loss decreases. Two immunizations with either i.m. or i.n. route protected immunized mice against virus challenges without any disease symptoms. Systemic antibody responses were found to be durable up to six month: IgG levels were not significantly different in the first three months but dropped in six months. However, the neutralization activity and hemagglutination inhibition (HAI) titers were not dropped significantly, demonstrating the durability of the protective antibodies. Because of the high immunogenicity and time-efficient egg-independent production (a few weeks not several months), stHA nanoclusters have potentials to be developed into a new generation of influenza vaccines, particularly for fighting an emerging influenza pandemic.
Jaap Goudsmit
Janssen Prevention Center, The Netherlands and USA
Title: Universal pandemic and seasonal Influenza vaccine design: directing the antibody repertoire
Time : 12:55-13:20
Biography:
Jaap Goudsmit is Global Head of the Janssen Prevention Center, a Center of Excellence launched at the start of 2015 within Janssen Research & Development, part of the Pharmaceutical Companies of Johnson & Johnson. In this role, he is responsible for driving the development and implementation of innovative strategies for disease prevention, focusing on the chronic, non-communicable illnesses that are on the rise in our aging populations. He joined the Janssen R&D Senior Leadership Team on January 1, 2015.
Abstract:
Seasonal Influenza vaccines have a variable and limited breadth of protection primarily due to the dominant dependence on the induction of hemaglutination inhibiting (HAI) antibodies. HAI antibodies bind to the head of the hemaglutinin (HA) molecule. We discovered somatically mutated antibodies of the VH1-69 lineage to the stem of the HA molecule shortly after influenza vaccination. These antibodies were broadly protective against influenza group A1, A2 and B viruses, in case of influenza A due to virus neutralization (fusion inhibition) and in case of B viruses due to antibody-dependent cellular cytotoxicity (ADCC). Comparing the CR9114 epitope (Dreyfus et al, Science 2012) with epitopes of HIV and HCV binding to antibodies of the VH1-69 lineage, attachment to the antigen is largely defined by a conserved hydrophobic CDR2 region. Subsequently we developed a HA stem trimer with the capability to tightly bind to a Fab of CR9114. The paratope of CR9114 was shown to bind to the HA stem trimer in a similar way (CDR3 & CDR2 dominance) as to full length HA. The HA stem trimer protected mice completely against both H1N1 and H5N1. In cynomolgus monkeys, the HA stem trimer reduced fever following H1N1 challenge and elicited broadly reactive stem-directed antibodies. These data provide proof-of-concept for design of an universal influenza vaccine based on directing the antibody repertoire.
- Track 4- Evolution and Epidemiological aspects of Influenza, Track 7: Reassortment and Reverse Genetics, Track 14:Animal flu-ecology, Track 16:Influenza Lung Immunology: Major diseases
Chair
Nicolas Noulin
hVIVO, UK
Session Introduction
Nicolas Noulin
hVIVO, UK
Title: Influenza. The same virus but a very different illness if you are young or old
Time : 09:00-09:30
Biography:
Nicolas has completed his PhD in immunology and molecular Biology at the age of 27 years from Orleans University (France) and postdoctoral studies from Institut Pasteur in Paris. He is Principle Virologist at hVIVO, a company pioneering a technology platform which uses human models of disease.
Abstract:
Respiratory viruses are among the most common causes of hospitalisation and are a particular threat to vulnerable populations such as the elderly. In this study the Human Viral Challenge Model of infection was used to investigate the immune response to a GMP produced wild-type A/Perth/16/2009 (H3N2) Influenza virus in healthy adults of different age classes.
After completion of the pre-clinical phase, a dose ranging titration clinical study was carried out in young healthy adults to select the most suitable safe titre of virus with a reproducible profile of pathogenicity. In the next phase the chosen dose was used to address the relationship between the age of infected subjects and the profile of influenza illness. Sero-suitable volunteers were inoculated with A/Perth/16/2009 virus in a quarantine facility and divided into two age groups: 18 to 45 and 46 to 64 years old. The development of symptoms and progression of infection were monitored for 8 days to assess parameters such as safety, clinical symptoms and virus shedding. Seroconversion was evaluated during a follow up visit at day 28 post infection.
The progression of the influenza disease was found to be different between the younger and older subject groups in terms of the profile of infection and the time of onset, time to peak, intensity and resolution of symptoms either by self-assessment using a standardised diary card (which has been used for over 15 years and in approximately 2000 subjects) or through diagnosis by a study physician, and in terms of virus shedding, measured by cell infectivity and molecular assays.
Results from this study will allow better understanding of the influenza virus in the community and will help in the development of new vaccine strategies and therapeutics for populations at risk, such as the elderly.
Yanbo Yin
Qingdao Agricultural University, CHINA
Title: Epidemiological analysis of H9N2 virus in China
Time : 09:30-09:55
Biography:
Yanbo Yin has completed his PhD from China Agricultral University. Member of avian diseases branch, Executive member of veterinary pathology branch, Chinese Association of Animal Science and Veterinary Medicine; The avian diseases prevention duty expert of Shandong Modern Agricultural Technology & Industry System. He is a professor of Qingdao Agricultral University and has trained more than 30 graduate students. He had published more than 200 peer-reviewed papers in English and Chinese.He is the Member of avian diseases branch, Executive member of veterinary pathology branch, Chinese Association of Animal Science and Veterinary Medicine;The avian diseases prevention duty expert of Shandong Modern Agricultural Technology & Industry System
Abstract:
In our lab, systemic surveillance and epidemiological investigation on H9N2 influenza were conducted. From January 2008 to August 2014, 6569 clinical samples had been collected and tested, and the positive rate of H9N2 influenza was 25.12%. More than 1,000 H9N2 virus strains were isolated. The genome sequences of the virus were determined, and the biological characters were tested. The results showed the mutation speed of HA gene became faster, new clade virus were emerging nearly year by year. Different clade virus was circulating at the same time and same location. The H9N2 virus isolated after 2008 displayed higher virulence to embryonated eggs, and the virulence with higher virulence in embryonated eggs also showed higher pathogenicity in chickens, and caused systemic infection. The antigenicity of H9N2 changed quickly, and formed different antigenic groups, some of which showed significant antigenic difference, compared with earlier vaccine strains. Our study also showed when HA amino acid sequence mutations reached a point (more than 7%), the antigenicity change could be significant. The study results emphasized that the vaccine strain should be updated in a timely manner through surveillance and accompanying laboratory evaluation of contemporary viruses for antigenic similarity with existing vaccine strains, and the genetic and pathogenic variation of H9N2 virus should be closely monitored.
Mohammed N. Al-Ahdal
King Faisal Specialist Hospital and Research Center, Saudi Arabia
Title: Characterization of H5N1 influenza A virus that caused the first highly pathogenic avian influenza outbreak in Saudi Arabia
Time : 09:55-10:20
Biography:
Mohammed N. Al-Ahdal (a Bio-Pharmacist) has completed his Ph.D. in Microbiology and Immunology from the State University of New York at Buffalo in 1985. He is the now the Chairman of the Department of Infection and Immunity at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, where he is also a Principal Scientist. He is a Professor of Microbiology and Immunology at the College of Medicine of Alfaisal University in Riyadh, Saudi Arabia and an Adjunct Professor at Sassari University in Italy and at Brunel University in the U.K. He has published more than 105 papers in reputed journals and serving as an editorial board member of some scientific journals.
Abstract:
Saudi Arabia has experienced a highly pathogenic avian influenza (HPAI) H5N1 outbreak in domesticated birds in 2007. From this outbreak, we sequenced forty-three HA and forty-one NA genes of HPAI-H5N1 viruses and performed phylogenetic analyses to compare these sequences with those of other viruses available in the public databases. Molecular characterization of the H5N1 viruses revealed two genetically distinct clades, 2.2.2 and 2.3.1. Amino acid sequence analysis of HA gene indicated that virus from 2.2.2 contained the sequence SPQGERRRK-R/G at the cleavage site, while from 2.3.1 contained the sequence SPQRERRRK-R/G. Additionally, we identified a few mutations with amino acid substitutions, such as M226I mutation at N-link glycosylation site in two of the isolates, which could affect receptor specificity as well as viral pathogenicity. Amino acid sequence of NA gene showed a 20-amino-acid deletion (positions 49–68) in the NA stalk region, required for enhanced virulence of influenza viruses and its adaptation from wild birds to domestic chickens. Relaxed clock and Bayesian Skyline Plot analysis based on HA and NA genes of our isolates and closely related global representatives indicated lower substitution rates (2.036X10-3 and 2.072X10-3 substitutions/nucleotide/year) when compared with earlier reports (4.23X10-3 and 4.27X10-3 substitutions/nucleotide/year). As close contact between humans and birds is unavoidable, there is a need of a thorough understanding of the epidemiology, factors affecting the spread of the virus and of the viral molecular characteristics of H5N1 viruses circulating in the region.
Devanshi Gohil
Haffkine Institute for Training, Research and Testing, India
Title: Genetic Characterization of co-circulating Influenza A Viruses in the Pandemic (2009-2010) and Post Pandemic (2010-2011) periods in Mumbai
Time : 10:35-11:00
Biography:
Devanshi Gohil is a Research Scholar currently pursuing Doctorate of Philosophy in Medical Microbiology on “Molecular characterization of 2009 H1N1 pandemic influenza & seasonal influenza viruses from patients in Mumbai” at Haffkine Institute for Training, Research and Testing, under Maharashtra University of Health Sciences, Nashik, India. She has done her post-graduation studies in Microbiology from University of Mumbai, India. Presently, she is working as Project Coordinator on National Project entitled Laboratory Based Influenza Surveillance Plan India: Under Integrated Disease Surveillance Project (IDSP) Avian Influenza Lab Network, run by National Center for Disease Control, Government of India, New Delhi, India. She has 7 publications to her credit in National and International journals.
Abstract:
Pandemic influenza A (H1N1) 2009 virus was first detected in May 2009 initiating the pandemic in India. Influenza A viruses has the ability to evade the immune response through the acquisition of genetic changes. Understanding the multiple lineages of influenza virus variants is necessary in lieu of co-circulation of influenza A (H1N1) pdm 09 and seasonal influenza A (H3N2) virus in Mumbai, a global transition hub. However, genetic information of circulating influenza strains in Mumbai is limited. In the present study, we performed molecular and evolutionary analysis of these co-circulating viruses isolated from patients with during August 2009 – March 2011. Positive samples were cultured and the viral genomes for HA and NA were analyzed for both seasonal and pandemic isolates. Molecular analysis revealed substantial sequence variations in both pandemic and seasonal influenza A viruses. HA1 sequences of pandemic isolates were conserved at the receptor-binding site, while variations in the amino acid substitutions at the antigenic sites resulted in the changes at the N-linked glycosylation sequon. In pandemic isolates, amino acid substitutions in the NA gene were dissociated with the catalytic or framework sites. Seasonal Influenza A virus exhibited antigenic drift. Phylogenetic analysis of the HA and NA genes of pandemic and seasonal isolates illustrated their evolutionary closeness or drift with their concomitant prototype vaccine strains respectively. Studies like ours aid in identifying the variations in the circulating influenza virus strains, as well as spot emerging variants, thus abetting a vigilant control over the disease.
Tony Velkov
Monash University
Australia
Title: Molecular characterization of the hemagglutinin receptor-binding specificity of avian influenza viruses: predicting the jump across the species barrier
Time : 11:00-11:25
Biography:
Tony Velkov completed PhD in 2000 from Monash University. His anti-infective discovery research is at the leading edge globally. He was awarded a NHMRC Research Fellowships in 2006, 2011 and 2014. The quality and impact of his independent research was recognized by the NHMRC with an Excellence Award in 2011. He has published over 50 papers in high-caliber journals, 3 book chapters and 15 conference presentations. The dynamic team he leads consists of 3 postdocs, 3 RAs and 9 PhD students. Over the last 6 years, he has obtained >$9M funding from the NIH, NHMRC and foundations.
Abstract:
Influenza is a constant global burden to human health. Seasonal influenza results in significant infections and death, cycling through both hemispheres. On occasion, a novel avian influenza virus crosses the species barrier from birds to humans resulting in an influenza pandemic. The threat of pandemic avian influenza continues with H5N1 and H7N9 consistently infecting humans. In order to evolve from its avian form and gain the pandemic potential for increased transmissibility between humans, the Hem-Agglutinin (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) penta-saccharide receptor analogs to ascertain the correlation between the binding assay data and the interactions within the receptor binding pocket. The present findings provided a structure-recognition perspective for the receptor binding properties of the novel avian H10 influenza HA.
Mpho Seleka
National Institute for Communicable Diseases, South Africa
Title: Circulating patterns of influenza B in South Africa: 2005-2014
Biography:
Mpho Seleka has completed Master’s of Medical Science Virology from Stellenbosch University, Faculty of Health Sciences, Department of Pathology, at a Division of Medical Virology. She is a Medical Scientist conducting influenza research (genome sequencing) and surveillance at National Institute for Communicable Diseases (NICD), a division of National Health Laboratory Services (NHLS).
Abstract:
In this study, we aim to describe the circulation patterns of the influenza B/Victoria and B/Yamagata lineages in South Africa and to determine the factors associated with hospitalization for SARI following infection with influenza B/Victoria or B/Yamagata lineages. Data for influenza B in South Africa are limited and the molecular epidemiology was previously described for the period of 1998-2001. The study enrolled patients from three influenza surveillance programs (Viral Watch, SARI and ILI) running in South Africa between year 2005 and 2014. Initially, starting from 2005 to 2008, influenza was diagnosed through virus isolation and antigenic characterization. From 2009, the technology of use was changed to real-time PCR assays. Influenza B vaccine strains recommended for the Southern Hemisphere were mismatched to the dominant circulating lineage in 2005, 2008, 2009 and 2011. Factors associated with infection with a specific influenza B lineage were assessed using the Fisher’s exact test. P-values <0.05 were considered to be statistically significant. Analysis was performed using STATA 13. In SARI cases, the overall frenquency of B/Victoria lineage (181/286 [63.3%]) was higher than that of B/Yamagata lineage (105/286 [36.7%]) from the year 2005 to 2014. The highest incidence of influenza B associated with severe lower respiratory tract infections was seen in the age group 0 to 4 (199/482 [41%]), followed by the age group 25 to 44 (146/482 [40%]), and the age group +65 has the lowest incidence (22/482 [5%]). The overall HIV incidene in the SARI case with influenza B is 99/235 (42%).
Biography:
Sherwin Morgan completed his respiratory care training from Malcolm X College of Respiratory Care in Chicago, IL. He is an advanced respiratory care practitioner with the National Board for Respiratory Care in the United States. He is Clinical Practice and Development /Educator/Research Coordinator for the Department of Respiratory Care Services, Section of Pulmonary and Critical Care Medicine at the University of Chicago Medicine. He has published more than 25 peer review papers in multiple medical journals. He has designed, engineered, and collaborated with a number of research studies with the pulmonary medicine department.
Abstract:
Heliox, a helium-oxygen gas mixture, has been used for many decades to treat obstructive pulmonary disease. The lower density and higher viscosity of heliox relative to nitrogen-oxygen mixtures can significantly reduce airway resistance when an anatomic or partial air-flow obstruction is present. Respiratory infections caused by coronavirus / rhinovirus-enterovirus range from the common cold to severe acute respiratory distress syndrome (SARS). In infants, respiratory syndromes can cause bronchitis, viral bronchiolitis, and pneumonia in variable combinations and may produce enough air-flow obstruction to cause respiratory failure. These viral strains are now documented to come from multiple viral agents and continue to mutate into new strains. I present the case of a 10-month old Hispanic male treated with high flow nasal cannula and heliox to avoid intubation. Before heliox the patient was tachypnea 60 – 70 breaths/min and would desaturate to 84% as measured by pulse oximetry with suprasternal chest retractions. After heliox 70/30, his respiratory rate fell 31 to 38 breaths/min. Nutritional support was implemented on day 1 of heliox administration. He was maintained on heliox either 60/40 or 70/30 for 48 hours and heliox discontinued on day three. He was discharged from PICU on day 10 and discharged from the hospital 7 days later. The benefit of heliox itself appeared to be immediate and served as a bridge to support the patient while time and pharmacologic measures took effect and an underlying infection abated.
Hongxin Zhao
Influenza Surveillance Section Respiratory Diseases Department Centre for Infectious Disease Surveillance and Control (CIDSC) Public Health England UK
Title: Epidemiological and virological characteristics of acute respiratory outbreaks during 2014/15 influenza season in the UK
Biography:
Hongxin Zhao is a Senior Scientist working in the Influenza Surveillance Section, Respiratory Diseases department, Public Health England, Colindale, London, UK. He has completed his PhD from University of Plymouth, UK.
Abstract:
The UK has an established respiratory outbreak reporting system used to monitor the activity and impact of influenza. The 2014/15 season has been dominated by the early circulation of A(H3N2). Outbreak reporting from week 40/2014 to 05/2015 has shown 444 acute respiratory outbreaks; 73% (324/444) in elderly care homes, 14% (62/444) in schools, 12% (54/444) in hospitals,. This compares to 122 outbreaks over the whole of 2013/14, 478 in 2012/13 and 230 in 2011/12. Reports of respiratory outbreaks started to increase from week 49/2014, and peaked in week 03/2015. Of 193 outbreaks with testing information, 90% (174/193) were due to influenza A, Fifty (11%) outbreaks reported fatal cases all in care homes. Fatal case numbers ranged from 1 to 17 (CFR 2.2% to 66.7%). Influenza vaccine uptake was available for 87 care homes with a median uptake of 95.0%, (range 11.9% to 100%). Of 42 care home outbreaks with complete information, all were laboratory confirmed to be associated with influenza (26 A(H3), 15 A(not-subtyped), 1 A(H1N1)pdm09 and 1 B). Influenza vaccine effectiveness (VE) could be calculated for 23 outbreaks in care homes with an overall estimated crude VE of -67.8% (range -384.6% to 100%). The higher numbers of reported influenza A confirmed outbreaks in care home settings in 2014/15 in often highly vaccinated populations compared to the previous three seasons was consistent with the pattern of influenza activity observed, where a drifted A(H3N2) variant has emerged and become the dominant strain.
Gloria Ramirez-Nieto
Universidad Nacional de Colombia
Colombia
South América
Title: Genetic variability of SIV circulating in commercial farms from Colombia, between 2008-2013
Biography:
Gloria Ramirez-Nieto has a degree on Veterinary Medicine from the National University of Colombia, a MSc on Veterinary Microbiology from the Royal Veterinary College, University of London and a PhD from the University of Maryland, College Park. She is currently Associate Professor at the School of Veterinary Medicine, National University of Colombia.
Abstract:
In Colombia, swine influenza virus has been present for over forty years, but only until recently viral isolation of classic and pandemic H1N1 swine influenza viruses demonstrated co-circulation of these viruses in the swine population from the main swine producing regions of the country. There was a clear predominance of the pandemic H1N1 subtype after the 2009 pandemic, but a lack of knowledge about the molecular changes at the virus level due to the appearance of this novel virus in a naïve non-vaccinated population. In this study an analysis of the variability at the nucleotide and amino acid level of the sequence of the hemagglutinin (HA) and neuraminidase (NA) genes of swine influenza viruses reported in Colombia between 2008-2013, was performed. The main focus was to look for changes of evolutionary significance, and phylogenetic trees were constructed accordingly to establish evolutionary relationships with swine influenza virus reported worldwide. Analysis of the HA and NA genes of the Colombian H1N1 swine influenza viruses showed that these were closely related to American and Asian strains. Molecular analysis revealed changes representing synonymous and non-synonymous mutations, and the changes that were associated with non-synonymous mutations, have not yet been reported as a cause of change in the antigenicity of these proteins so far. The positions in the sequences of HA and NA with evolutionary significance, were related to differences associated with the affinity and avidity for the recognition of different conformation of sialic acid receptors in the host cells.
- 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.