Day 22 :
- Track 1: Influenza Vaccines: Designs and Developments Track 3: Influenza: Causes, Symptoms and Treatment Track 5:Influenza Vaccines : Safety and Effectiveness Track 7:Advances in Viral Detection and Identification Technologies Track 9:Host Genetics of Infection and Immunology
Chair
Palayakotai Raghavan
Nanorx Inc, USA
Co-Chair
Jerzy Radecki
Institute of Animal Reproduction and Food Research of Polish Academy of Science, Poland
Session Introduction
Palayakotai Raghavan
Nanorx Inc, USA
Title: Controlling viral infection with Metadichol
Biography:
Palayakotai Raghavan is CEO and Founder of Nanorx INC. He completed Ph.D in Organic Chemistry from Oregon State University (1979) and M.S in Chemistry (1972) from I.I.T Mumbai, India. He has worked on drug discovery for over 25 years at Columbia University, Max-Planck Institute, Germany, Ciba-Geigy (now Novartis) and Boehringer Ingelheim. He has over 12 patents and another 15 pending patent applications.
Abstract:
Metadichol (US patent 8,722,093) is a Nano emulsion of long-chain alcohols found in many foods. It is commonly called Policosanol and is present in foods such as rice, sugar cane, wheat, peanuts Metadichol acts on Nuclear Vitamin D receptors (VDR) (US patent 9,006,292) that are present in cells throughout the body to stimulate the immune system and inhibit a variety of disease processes, resulting from viral infections.We tested for antiviral activity of Metadichol® in Vero and MDCK cells infected with Influenza A, H1N1, Human Respiratory Syncytial viruse, Dengue, Chikungunya and. Ebola, Marburg. In addition, we tested the efficacy of Metadichol® in preventing cell death caused by Adenovirus, Tacaribe Mammarena virus, Rift Valley Fever virus, SARS coronavirus, Japanese Encephalitis virus, West Nile virus, and Yellow Fever virus. In the in vitro assays, Metadichol showed no cytotoxicity and strongly inhibited cell death caused by each of the viruses tested. Metadichol is a safe and effective inhibitor of enveloped viruses in humans. Since it is known to bind to the vitamin D receptor (VDR) (US patent 9,006,292), its mechanism of action likely involves the competitive displacement of virus particles from VDR’s on host cell membranes. Because it consists of natural components of common foods and has no known negative side effects, Metadichol has the potential to serve as a novel, broad-spectrum antiviral treatment for Dengue, Ebola, Zika, H1N1, SARS, Chikungunya and other enveloped viruses.
Marcus Hartmann
Cilian AG, Germany
Title: CiFlu®: Development of a novel subunit influenza vaccine candidate based on the ciliate performance expression system
Time : 12:05-12:30
Biography:
Marcus Hartmann has spent his scientific career investigating protozoan organisms, particularly Ciliates. He worked for the central research department of Aventis, Frankfurt (Germany) and was a postdoc in an academic working group at the University of Münster. His postdoctoral study dealt with research in the field of commercial applications of protozoan organisms. Based on his extensive scientific experience in the field Ciliate biotechnology, he founded Cilian, and since then he has headed the Company’s R&D team. Marcus Hartmann is the author of numerous scientific publications, recitations and patents in the area of Ciliate biotechnology. One of the main breakthrough of his team was the first-ever production of therapeutically usable proteins in Ciliates.
Abstract:
The critical annual manufacturing process for seasonal influenza vaccine based on embryonated chicken eggs, involves numerous steps and takes on average 6 to 8 months to complete. This often means that vaccine is only available late into the flu season. The timely availability of an effective influenza vaccine, at or before the flu season starts, is even more acute for vulnerable highest risk groups such as persons 65 years of age and older. The lack of timely availability of seasonal/pandemic vaccine has raised significant questions about the utility of the current, antiquated, cumbersome, expensive and unsafe manufacturing platform involving chicken eggs. Safety concerns about cell culture based virus proliferation processes called also alternative flu vaccines production processes into question. Now new recombinant antigen manufacturing platforms were postulated to reduce production time and costs. Cilian’s flu vaccine CiFlu® is a cost-effective subunit vaccine based on the heterologous expression of recombinant Influenza hemagglutinin (rHA) in the ciliate Tetrahymena. Utilizing its CIPEX-System as such a manufacturing platform, Cilian has successfully demonstrated repeated expression of rHA at high yield: four subunit vaccines has been expressed and shown to be functionally active. Mice were first immunized with the monovalent rHA. HA antibodies were harvested and its ability to inhibit the respective influenza strain was tested. The results demonstrated comparable or better efficacy (in vivo inhibitory immunogenicity) to monovalent vaccine from chicken eggs. Cilian meanwhile received a positive scientific advice from the German Paul Ehrlich Institute for CiFlu® and is developing a comprehensive clinical plan.
Sherwin Morgan
University of Chicago Medicine, USA
Title: Global recognition of influenza-like severe respiratory illness
Time : 12:30-12:55
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:
Clinical recognition of severe respiratory illness (SRI) is difficult. Influenza-like respiratory illness often masquerades as asthma, especially in patients with and without pre-morbid pulmonary disease. Because the initial differential diagnosis includes asthma, this can lead to treatment confusion and an underestimation for the primary cause for SRI. Viral bronchosplasm is difficult to ameliorate air-flow obstruction (AFO) with bronchodilator therapy that is refractory to beta-agonist and steroid therapy. This may lead to patients requiring supportive respiratory care. Viral SRI is now documented to come from multiple viral sources and appear in different packages. These viruses are high pathogenic and attack the bronchial wall structure causing hypercarbic respiratory failure. These viral infections are now documented as being the etiology of global epidemics and pandemics. In August 2014, there was an increase in SRI that was associated with Enterovirus EV-68 which was reported in 41 states across the United States. The Center for Disease and Control (CDC) received over 2600 samples, 36% positive for EV-68. Viral illnesses have a huge impact on global resources and finances. Clinical diagnoses via respiratory viral panel and chest radiography may be relevant. Newer treatment plans for SRI include the use of high flow nasal cannula (HFNC) and heliox. Failure to recognize SRI may lead to hypercarbic respiratory failure where the support therapy is ventilator, pruning, nitric oxide, ECMO. This can lead to complications such as; ARDS, kidney and other organ failure and severe acute respiratory syndrome. More study is needed to understand the relationship between SRI-AFO.
Hanna Radecka
Polish Academy of Science, Poland
Title: Electrochemical immunosensors: Universal tools for rapid detection of viruses
Time : 12:55-13:20
Biography:
Hanna Radecka was graduated from the Department of Chemistry of Nicolaus Copernicus University in ToruÅ„ in 1978. She was a Visiting Scientist at the Hokkaido University in Sapporo and at the University of Tokyo. Since 1998, she is working at Department of Biosensors of the Polish Academy of Sciences in Olsztyn. In 2011 she received the title of Professor of Analytical Chemistry and was nominated as the Head of Laboratory of Bioelectroanalysis. Currently she is working on the development of the new biosensors for determination of avian influenza viruses, possible biomarkers of Alzheimer’s and other neurodegenerative diseases present in human plasma.
Abstract:
Here, we report examples of successful developing of several type of immunosensors destined for the detection of Highly-Pathogenic Avian Influenza type H5N1 virus (HPAI) spreading among wild and domestic birds. The immunosensor were developed by the successive modification of gold as well as glassy carbon electrodes. The whole antibody or their fragments have been applied as the sensing elements. The complex between virions and specific antibody adsorbing on a surface of an electrode forms an insulating layer. This phenomenon, which is a base of ion-channel mimetic type of immunosensors, can be monitored by the electrochemical impedance spectroscopy (EIS) in the presence of [Fe(CN)6]3-/4- as a redox marker. The another type of immunosensors are based on redox active layers incorporated di-pyrromethene-Cu(II). The changes of electrochemical parameters of redox centers upon target analyte binging are the base of analytical signal generation. The both type of immunosensors displayed better sensitivity towards viruses as well as antibodies in comparison to ELISA; they are also very selective. The matrix from hen sera has no influence on the immunosensors performance. In addition, very small analyzed sample volumes (10 µl) are needed. After miniaturization, they keep excellent analytical parameters. Therefore, immunosensors presented could be recommended for the direct electrochemical detection of viruses as well as antibodies in the natural physiological samples.
Jerzy Radecki
Polish Academy of Science, Poland
Title: Electrochemical genosensors based on redox active monolayers: Characterization and applications
Time : 14:05-14:30
Biography:
Jerzy Radecki is the Professor of Analytical Chemistry and currently working as Head of Department of Biosensors of IARFR PAS in Olsztyn. His research interest concerns the developing of new sensors and biosensors based on the intermolecular recognition processes occurring at the border of the aqueous and organic phase. Particularly, he is interested in functionalization of surface of solid electrodes with “host” molecules, which are responsible for “guest” molecules (analytes) recognitions. He is working on not only analytical aspects of developed sensors but on the elaboration of the mechanism of analytical signal generation as well.
Abstract:
Here we report on electrochemical genosensors devoted for detection of influenza virus H5N1 gene sequence. Using ssDNA decorated with redox active units such as Co(II)-porphyrin or 3-iron bis (dicarbiollide), the detection limit in the fM range has been achieved. The strategies based on dipyrromenthene Cu(II) redox active monolayer or phenanthroline-Epoxy-Fe(III) complexes have been also applied for the development genosensors destined for detection of DNA as well for RNA derived from Avian Influenza viruses. They have been working based on the new “ion barrier switch-off” mechanism of analytical signal generation. To face of the need of systems for simultaneous determination of few markers of one disease coming from medical diagnosis, we have developed a novel dual DNA electrochemical sensor with “signal-off” and “signal-on” architecture for simultaneous detection of two different sequences of DNA derived from Avian Influenza Virus type H5N1 by means of one electrode. Two sequences of ssDNA characteristic for hemagglutinin decorated with ferrocene and characteristic for neuraminidase decorated with methylene blue were immobilized covalently together on the surface of one gold electrode. Taking into account the excellent analytical parameters of genosensors presented such as good sensitivity, selectivity and very low sample consumption, they could be recommended for future wide application for medical diagnostic as well as environmental control.
Farhid Hemmatzadeh
The University of Adelaide, Australia
Title: DIVA tests for avian influenza, which antigen must be chosen
Time : 14:30-14:55
Biography:
Farhid Hemmatzadeh joined The University of Adelaide as a senior lecturer of virology at the School of Animal & Veterinary Sciences in 2009. Previously, he was employed by Melbourne University since 2005 and Tehran universities as an associate professor since 1997. He has over 20 years experience in research and teaching at the field of animal viral diseases including herpesviruses, pestiviruses, retroviruses, parvoviruses and influenza viruses. Farhid has been involved in research, development and assessment of diagnostic test for animal viral diseases specially DIVA tests for poultry and large animals.
Abstract:
In last 15 years numbers of ELISA test were developed to differentiate influenza infected from vaccinated animals (DIVA). In most of the test the either viral associated infection antigens or heterologous Neuraminidase antigens were used to develop DIVA tests. One of the first attempts was non-structural 1 protein (NS1). The NS1-based ELISA was shown reliable results as a DIVA test in young chickens but the accuracy of NS1-based DIVA test decreases by the time and numbers of vaccination produces non-specific reactions. Nucleoprotein (NP) and conserved HA274–288 epitope were the others candidates for DIVA test but these two antigens didn’t show any values as DIVA ELISAs. By now the best antigen to develop DIVA-ELISA test is ectodomain of matrix 2 (M2e) protein. Relatively invariable nature of M2e protein across AIV strains and high level of expression of M2e protein on the surface of infected cells despite being low in copy number in a mature virions are the main properties that make M2e a suitable candidate for DIVA tests. Our studies on structure of M2e showed the tetramer form of M2e shows higher sensitivity and specificity to discriminate M2e antibodies in sera of infected birds from vaccinated or non-vaccinated birds.
Daniel Lingwood
The Ragon Institute of MGH, MIT and Harvard University, USA
Title: Multivalent influenza hemagglutinin promotes the immundominance of non-neutralizing antibody responses through reptatively constrained orientation
Time : 14:55 - 15:20
Biography:
Daniel Lingwood is an Assistant Professor at The Ragon Institute of MGH, MIT and Harvard and is a faculty member in the Virology Program at Harvard Medical School. He received his Ph.D. from the Max Planck Institute for Molecular Biology and Genetics, and conducted postdoctoral work at the Vaccine Research Center at NIH. Dr. Lingwood has garnered international recognition for his discovery that humans possess genetically-encoded antibody sequences that when properly oriented as germline B cell receptors, naturally engage conserved sites of viral vulnerability and serve as substrates upon which broadly neutralizing antibodies can be developed.
Abstract:
Much of the influenza virion surface is occupied by a dense array of trimeric hemagglutinin (HA) that functions to engage sialyl-oligosaccharide on a target cell. This dense packing of spike protein is also thought to restrict antibody access to the conserved HA stem epitope, a weakly immunogenic target for broadly neutralizing antibody (bnAb) responses against this virus. However, recent cryo-EM studies, have suggested that stem-directed bnAbs do not have restricted access to this site. To functionally define the source of weakened immunogenicity to the stem epitope, we compared stem specific antibody responses to three structurally-defined presentations of HA: soluble trimer, and ferritin nanoparticle 8mers displaying either the full-length trimer or stem/stalk region alone. Surprisingly, we found that while the nanoparticles were more immunogenic, only the soluble trimeric format elicited detectable stem-epitope directed antibodies upon initial exposure to antigen. We propose that antigen multivalency, a cornerstone of both vaccine design and viral architecture, imposes not only repetitive array to increase immunogenicity but also restricted antigen orientation, which can limit exploration of antigenic space, insuring that immunodominant non-neutralizing responses are non-linearly amplified during this process. Repetitive exposure to the soluble HA trimer eliminates reactivity to stem due to amplification of immunodominant non-stem responses; our work shows that multivalent HA display can achieves the same result within a single encounter. These data highlight a previously unrecognized mode of immune distraction and delineate the relationship between antigen valency and the target-specificity of the humoral response.
Yuri Vasiliev
Mechnikov Research Institute of Vaccines & Sera, Russia
Title: Challenges in development of chitosan-based adjuvants for influenza vaccines
Biography:
Yuri Vasiliev has completed his PhD from the Moscow Medical University in prepandemic avian influenza vaccines at the age of 24 years and started postdoctoral research at the Mechnikov Research Institute of Vaccines and Sera, Moscow. He became head of laboratory of experimental immunology at the age of 28 years and a year later was appointed as head of R&D for adjuvants, his current position at the Mechnikov Institute. He has published more than 50 works locally and internationally, with the top citations per single paper reaching 30 (bibliometrics via Web of Knowledge).
Abstract:
Chitosan-based formulations combine effectiveness, safety and economic feasibility, and have been studied as vaccine adjuvants and gene delivery systems. However, chitosan is an umbrella term for a very diverse group of glucosamine-based substances and their derivatives as well as adjuvants (e.g. solutions, particles). Lack of consensus on nomenclature and standardization approaches renders juxtaposition and reproduction of data across various studies nearly impossible, and underlying mechanisms of action for chitosan-based adjuvants remain largely unknown. Panels of chitosan substances and chitosan-based adjuvants (currently exceeding 50) have been created and characterized extensively using distinct methods (HPLC, NMR, etc.). Datasets generated from large-scale preclinical studies in various animal models demonstrate that principal chitosan characteristics (molecular weight and deacetylation degree) determine adjuvant properties through a very complex interaction. No single characteristic is responsible for high or low immunogenicity, effectiveness (lethal challenge model) and safety. Levels of serum and lung antibodies, IgG subclasses and certain cytokines and, thus, Th polarization also varied for different chitosans. Certain chitosans and derivatives (e.g., succinylated) were not immunogenic at all. Impurities (e.g., endotoxins, proteins) were challenging to evaluate due to interference from chitosan, however, did not have a critical effect on adjuvant properties. A universal chitosan-based adjuvant has been developed and successfully evaluated with various vaccines against influenza (subunit, cold-adapted, etc.) and other human and animal infections as well as in comparison with other adjuvants (aluminium-based, oil-in-water emulsions, etc.). Chitosan-based adjuvants tailored for certain types of influenza vaccines (100-fold increase of immunogenicity) and complex formulations are also being studied.
Yuri Vasiliev
Mechnikov Research Institute of Vaccines & Sera, Russia
Title: Challenges in development of chitosan-based adjuvants for influenza vaccines
Time : 15:20-15:45
Biography:
Yuri Vasiliev has completed his PhD from the Moscow Medical University in prepandemic avian influenza vaccines at the age of 24 years and started postdoctoral research at the Mechnikov Research Institute of Vaccines and Sera, Moscow. He became head of laboratory of experimental immunology at the age of 28 years and a year later was appointed as head of R&D for adjuvants, his current position at the Mechnikov Institute. He has published more than 50 works locally and internationally, with the top citations per single paper reaching 30 (bibliometrics via Web of Knowledge).
Abstract:
Chitosan-based formulations combine effectiveness, safety and economic feasibility, and have been studied as vaccine adjuvants and gene delivery systems. However, chitosan is an umbrella term for a very diverse group of glucosamine-based substances and their derivatives as well as adjuvants (e.g. solutions, particles). Lack of consensus on nomenclature and standardization approaches renders juxtaposition and reproduction of data across various studies nearly impossible, and underlying mechanisms of action for chitosan-based adjuvants remain largely unknown. Panels of chitosan substances and chitosan-based adjuvants (currently exceeding 50) have been created and characterized extensively using distinct methods (HPLC, NMR, etc.). Datasets generated from large-scale preclinical studies in various animal models demonstrate that principal chitosan characteristics (molecular weight and deacetylation degree) determine adjuvant properties through a very complex interaction. No single characteristic is responsible for high or low immunogenicity, effectiveness (lethal challenge model) and safety. Levels of serum and lung antibodies, IgG subclasses and certain cytokines and, thus, Th polarization also varied for different chitosans. Certain chitosans and derivatives (e.g., succinylated) were not immunogenic at all. Impurities (e.g., endotoxins, proteins) were challenging to evaluate due to interference from chitosan, however, did not have a critical effect on adjuvant properties. A universal chitosan-based adjuvant has been developed and successfully evaluated with various vaccines against influenza (subunit, cold-adapted, etc.) and other human and animal infections as well as in comparison with other adjuvants (aluminium-based, oil-in-water emulsions, etc.). Chitosan-based adjuvants tailored for certain types of influenza vaccines (100-fold increase of immunogenicity) and complex formulations are also being studied.
Manmohan Singh
Seqirus, USA
Title: History of emulsion adjuvants and their use in influenza vaccines
Biography:
Manmohan Singh, Ph.D. is currently the Head, Translational Research and Drug Product and Analytical Development within Seqirus. Prior he was Head of Technical Development (TD) within Novartis Vaccines in Holly Springs, NC USA. He joined NVD TD in 2012 and prior to that had spent 16 years in the Research Division of formerly Chiron and now Novartis Vaccines. He was part of the Chiron/NVD vaccines research team that over the years has developed several innovative antigen and adjuvant delivery technologies. He is a licensed Pharmacist and holds a Masters and a PhD in Pharmaceutics from the National Institute of Immunology, New Delhi India. Dr. Singh is the author of over 120 original research publications, editor of four books on vaccine research and development and is an inventor on over 47 issued patents.
Abstract:
TBA
Kathleen Hefferon
Cornell University,Canada
Title: Plant expression platforms for vaccine production
Biography:
Kathleen Hefferon received her PhD from the Department of Medical Biophysics, University of Toronto and continued her post-doctoral studies at Cornell University. Dr. Hefferon has worked on faculty at the Division of Nutritional Sciences at Cornell and has written two books on biopharmaceuticals in plants. She teaches and conducts research at both the University of Toronto and Cornell University. Kathleen has 4 patents, has edited 6 books, and has multiple research publications. Kathleen currently lives with her family near Ithaca NY.
Abstract:
Plant made biologics have elicited much attention over recent years for their potential in assisting those in developing countries who have poor access to modern medicine. Additional applications such as the stockpiling of vaccines against pandemic infectious diseases or potential biological warfare agents are also under investigation. Plant virus expression vectors represent a technology that enables high levels of pharmaceutical proteins to be produced in a very short period of time. Recent advances in research and development have brought about the generation of superior virus expression systems which can be readily delivered to the host plant in a manner that is both efficient and cost effective. The following presentation describes recent innovations in plant virus expression systems and their uses for producing biologics from plants.
- Track 2:Pathogenicity of Influenza Virus Track 4:Global Market for Influenza Vaccine Manufactures Track 6:Antiviral Drug Development and Treatment Strategies, Including Vaccination Track 10:Influenza Lung Immunology: Major Aspects Track 11:Animal Flu-Ecology
Chair
Reza Nassiri
Michigan State University, USA
Co-Chair
Hanna Radecka
Polish Academy of Science, Poland
Session Introduction
Tatyana Ilyicheva
Vector State Research Center of Virology and Biotechnology, Russia
Title: Influenza in Russia in 2014-2016
Time : 11:25-11:50
Biography:
Tatyana Ilyicheva has completed her PhD at the age of 33 years from Lobachevsky State University of Nizhni Novgorod and postdoctoral studies from Vector State Research Center of Virology and Biotechnology. She is the head of influenza laboratory of Vector Center and associated professor of Novosibirsk State University. She has published more than 20 papers in reputed journals.
Abstract:
In 2014–2015, fifteen influenza A(H3N2), two A(H1N1pdm09), and one B (Yam) virus strains were isolated from autopsy and clinical material from individuals with severe course of influenza-like disease. In 2015–2016, we isolated 105 influenza A(H1N1pdm09), one influenza A(H3N2) viruses from autopsy material, and 226 influenza A(H1N1pdm09) and four influenza A(H3N2) viruses from nasopharyngeal swabs. Virus A/Khabarovsk/6/2015 (H3N2) showed reduced sensitivity to oseltamivir (18-fold below normal). All other viruses exhibited normal inhibition by oseltamivir and zanamivir. Ð(H1N1pdm09) viruses were antigenically characterized as A/California/07/2009-like. Their HA gene sequences fell into genetic group 6B, the predominant genetic group. H3N2 isolated viruses were characterized as A/Hong Kong/4801/2014-like and A/Switzerland/9715293/2013-like, their HA gene sequences belong to genetic groups 3C.2a and 3C.3a, respectively. Influenza B virus was antigenically similar to B/Phuket/3073/2013, its HA sequence belongs to genetic group Y3. In 2014, we isolated influenza A(H5N8) virus from a Eurasian wigeon (Anas penelope) in Eastern Siberia. The strain A/wigeon/Sakha/1/2014 (H5N8) was shown to be pathogenic for mammals. It is similar to the strains that caused outbreaks in wild birds and poultry in Southeast Asia and Europe in 2014. In spring 2015, we isolated tree influenza A(H5N1) viruses from wild birds in the South of Western Siberia. All strains were pathogenic for mammals and showed reduced anti-neuraminidase drug sensitivity. In total 3,888 human blood serum samples were collected in October–November, 2014 in Russia. The presence of antibodies to influenza viruses in the sera was tested in hemagglutination inhibition test. None of the samples produced positive results with influenza A(H5N1), A(H5N8), and A(H7N9) viruses.
Melia Magnen
Institut National de la Santé et de la Recherche Médicale, France
Title: Kallikrein-related peptidase 5 contributes to H3N2 influenza virus infection in human lungs
Time : 11:50-12:15
Biography:
Melia Magnen is currentlypersuing her PhD at the CEPR, Tours, France.
Abstract:
The cleavage of the influenza A virus hemagglutinin (HA) by host serine-proteases is essential for viral infectivity. Several serine proteases of the kallikrein-related peptidase (KLK) family are produced and secreted by the airways and we investigated whether KLK1, 5 and 14 were involved in seasonal IAV infection. Expression of KLK1, 5 and 14 was assessed at the protein levels, in human tracheal aspirates from flu patients in intensive care unit, using ELISA. Primary human bronchial epithelial cells (hBEC) cultured at the Air-liquid interface were infected with IAV and the expression of KLKs was analyzed by RT-qPCR and flow cytometry. We also investigated in vitro if KLK1, 5 and 14 were able to cleave HA precursors. Finally, inactivated virions (mouse adapted A/Scotland20/74, H3N2) were treated with KLKs and the infectiveness was determined in MDCK cells and in mice. Flu infection selectively increased expression of KLK5 in hBEC and its secretion in the human airways. KLK1, 5 and 14 were able to cleave in vitro HA precursor from several subtypes of influenza viruses. Furthermore, only the KLK5 treatment of H3N2 virions promoted IAV infection in MDCK cells. In mice, the treated virus led to severe infection with KLK5 treatment and to moderate one with KLK14 treatment. KLK1 virus treatment did not result in infection. Expression and secretion of KLK5 is specifically induced in airways upon flu. This induction likely contributes to the propagation of the virus in favoring its multi-cycle replication through activation of the HA precursor.
Essam Badawy
Minia University, Egypt
Title: The clinical characteristics and outcome of H1N1 pneumonia patients with and without acute renal injury
Time : 12:15-12:40
Biography:
Essam Badawy has completed his MD at the age of 34 years from Minia University, EGYPT and ITS THESIS studies from Cairo University School of Medicine. He is the director of Emergency Department, Hera General Hospital, JCI-Accredited governmental hospital, MOH, KSA. He is senior consultant Internal Medicine & professor of Internal Medicine & Immunology, Faculty of Medicine, Minia University. He has published more than 24 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Currently, little information exists about the impact of kidney injury and resource utilization in the form of renal replacement therapy in critically ill patients with H1N1 infections. 40 patients who were living inor visitors to Makkah region , admitted to the hospital and revealed confirmatory H1N1 infection, pneumonia and acute renal injury, were submitted to rRT-PCR. Severity of illness was assessed by using APACHE II, SOFA score, MOD score XR Chest score, PaO2/FIO2 and Co-morbidities were recorded. Acute renal injury is an adding impact of increasing the mortality rate of H1N1 pneumonia patients and may be related directly to the infection by this virus or complication to it which may be explained by severe hypoxia secondary to severe lung injury , multiorgan dysfunction. A high mortality in middle and old- aged patients with underlying medical co-morbidities was associated with higher symptoms severity, APACHE II, SOFA, MODS and XRC scores. Early recognition of the disease as well as prompt medical attention to provide opportunities aiming to limit the progression of the illness and to reduce the mortality. Prospective and controlled clinical trials are needed for claryfing the effectiveness of the early treatment and protection by using H1N1 vaccine.
Biography:
De-chu Christopher Tang is the Founder of VaxDome LLC and Vaxin Inc. (Vaxin’s nameplate was changed to Altimmune, Inc. in 2015 after merging with Immune Targeting Systems Ltd). He obtained his PhD in Microbiology from Indiana University in 1989. He carried out his postdoctoral work at Baylor College of Medicine, Duke University, and University of Texas Southwestern Medical Center. He joined the faculty at University of Alabama at Birmingham (UAB) in 1994; subsequently founded Vaxin Inc. on UAB campus in 1997; and was responsible for Vaxin’s daily operation as the Chief Scientific Officer until 2012. Dr. Tang was one of the pioneers during the development of DNA vaccines, noninvasive skin-patch vaccines, adenovirus-vectored nasal vaccines, adenovirus-vectored poultry vaccines, as well as the protective innate-adaptive immunity duo platform technology. He received the Wallace H. Coulter Award for innovation and entrepreneurship in 2000; and Vaxin Inc. was selected as a Tech Museum Awards Laureate in 2007. Dr. Tang was selected as a Distinguished Overseas Scientist by the South Korea KOFST Brain Pool Program in 2012; subsequently joined Chung-Ang University and International Vaccine Institute (IVI) in Seoul; and was appointed as a Scientist at IVI after the Brain Pool Program Award expired in 2013. He founded VaxDome LLC in Birmingham, Alabama, USA in 2014 and moved the company to Dallas, Texas, USA in 2015.
Abstract:
We report that intranasal administration of an E1/E3-defective (ï„E1E3) adenovirus serotype 5 (Ad5)-vectored influenza vaccine could induce seroconversion in human volunteers without appreciable adverse effects, even in subjects with pre-existing Ad5 immunity. Mice and ferrets were well protected against challenge by a lethal dose of an H5N1 avian influenza virus following intranasal instillation of an Ad5 vector encoding hemagglutinin (HA) in a single-dose regimen. Moreover, the ï„E1E3 Ad5 particle itself without transgene could confer rapid-sustained-broad protection against influenza by inducing an anti-influenza state in a drug-like manner, conceivably by activating a specific arm of innate immunity. An Ad5 vector encoding HA thus consolidates drug and vaccine into a single package, which allows the Ad5 backbone to induce protective innate immunity capable of conferring nearly-immediate and prolonged (e.g., 5 hours to 47 days) protection as the first wave against influenza; followed by HA-mediated adaptive immunity as the second wave before the innate immunity-associated anti-influenza state declines away. Overall, the work conceivably would foster the development of a novel noninvasive drug-vaccine duo platform technology capable of conferring rapid-sustained-broad protection in a wide variety of influenza settings, with neither the potential to induce drug resistance nor that to trigger harmful systemic inflammation.
Jacob A Dunga
ATBU Teaching Hospital, Nigeria
Title: Types of human influenza virus among patient at Abubakar Tafawa Balewa University Teaching Hospital (ATBUTH), Bauchi, Nigeria
Time : 12:40-13:05
Biography:
Jacob A Dunga has completed his MBBS at the age of 24 years from University of Maiduguri Teaching Hospital, Borno state and postgraduate fellowship in Pulmonology at National postgraduate medical college of Nigeria. He also has postgraduate diploma in management and master’s degree in health planning and management. He is senior consultant Physician (Pulmonologist) at ATBU Teaching Hospital and a visiting senior lecture with Gombe state University medical college. He is a member of ATS, ERS, PATS, and NTS. He has published more than 10 papers and has served as research coordinator for National Influenza surveillances and PMTCT
Abstract:
Human influenza is an acute respiratory illness resulting from infection with an influenza virus, it is ahighly infectious virus and can spread rapidly from person to person,and some strains are more pathogenic than others. Nigeria suffered waves of Highly Pathogenic Avian Influenza (HPAI) outbreaks that peaked twice in February 2006 and February 2007.The burden of Influenza is likely to be under estimated in Nigeria. This study is expected to monitor the occurrence of influenza in this part of the country, with the aim of providing a foundation for detecting outbreaks and pandemics, mapping out common strains or emergence of a novel strain of influenza so as to create an early warning system to trigger a rapid public health response and specific vaccine for common strains.This study is a cross sectional survey, our target populations were all adult and pediatric patient admitted at the pediatrics and internal medicine department of ATBUTH who has met the criteria for Cough, fever (>37 o C), nasal congestion and dyspnea. Samples collected over 12 months were analyzed using the polymerase chain reaction (PCR) at national influenza reference laboratory (NIRL).Detection and subtyping of influenza viruses in respiratory specimens was done. Overall 49% female samples and 51% males samples were collected, 5% of the samples collected tested positive for human influenza type A and B, 60% of the positive result were among the female samples where as 40% from the male samples, among the positive sample about 80% were positive for Human Influenza type A (Flu A), whereas 20% where positive for Human Influenza type B (Flu B). There were more cases of human influenza among the age group 1 - 5years equals 3% of total samples collected compared to 1% each for 6 – 25years and 26 – 45years, the incidence were found to be less or absent among those > 45years.
Nailya Klivleyeva
Institute of Microbiology and Virology, Kazakhstan
Title: Study on the circulation of influenza A virus in swine populations in Kazakhstan
Time : 13:50-14:15
Biography:
Nailya Klivleyeva is presently working in Institute of Microbiology and Virology, Kazakhstan.
Abstract:
Emergence of influenza virus A (H1N1)pdm in humans which is a complex reassortant of the swine-origin genotypes, emphasized the importance of worldwide surveillance for influenza virus in swine. 1293 biosamples (893 nasopharyngeal swabs and 400 blood serums) have been collected from swine in the small and large pig farms of the Almaty, Aktobe, Karaganda, Kostanaу, Pavlodar and North-Kazakhstan oblasts in 2014-2015. Primary screening of 893 biosamples (nasopharyngeal swabs), carried out in RT-PCR using AmliSens PCR test system produced by the Central Research Institute for Epidemiology (Moscow) showed the presence of genetic material of the influenza virus in 171 samples (19.15% of the total number of examined samples). Influenza A/H1 virus RNA was detected in 111 samples (12.43%), A/H3 virus RNA - in 10 samples (1.12%). These data indicate circulating influenza virus of mixed etiology in the swine population with a predominance of influenza Ð/Ð1 virus. As a result of primary infection of chicken embryos with 893 biosamples collected from swine in various regions of Kazakhstan, 22 infectious agents were isolated with the hemagglutination titres of 1:2-1:32 and infectious activity of 3.47-9.45 lgEID50/0.2ml. Identification in HAI and NAI assays of seven isolates from the Almaty (06/14 and 10/14), Karaganda (04/14 and 16/14) and Kostanaу (12/14, 23/14 and 24/14) oblasts enabled to attribute them to influenza A virus with the H1N1 antigenic formula. Serological analysis of 400 blood serums collected from healthy and sick swine in the pig-breeding farms to detect antibodies against influenza A/H1N1 and A/H3N2 virus was carried out with IEA and HAI assay. The greatest number of specific antibodies was detected against the influenza virus subtype A/H1N1.Thereby, the findings confirm the circulation of influenza Ð/Ð1N1 virus in the swine population on the territory of Kazakhstan, which indicates the need for a permanent virological examination of swine with the aim of the earliest detection of the potential pandemic influenza virus strain.
Mohammad Ali Daneshmehr
Iran University of Mediccal Sciences, Iran
Title: Herbal immune boosters: Valuable preventive means for international travelers flu
Time : 14:15-14:40
Biography:
Mohammad Ali Daneshmehr has studied pharmacy at Tehran University of Medical Sciences (TUMS), and graduated in 1990. He started career in Shahid Beheshti University of Medical Sciences (SBMU) as an instructor. In 1993 he pursued his studies in University of Manchester, UK in medicinal chemistry and got PhD (2001) on ligands in DNA minor groove. He has been working since, in different parts of Iran as founder of a number of pharmacy schools including Hamadan (UMSHA), Kermanshah (KUMS) and currently Iran University of medical Sciences (IUMS). Fields of interests includes natural products as lead compounds to find new drugs.
Abstract:
Acute respiratory tract infections are account for millions of lost effective work or school days, healthcare clinic visits, antibiotic prescriptions, hospital admissions and eventually morbidity or even mortalities. International tourism including religious pilgrimage to overcrowded destinations considerably increases the chance for dissemination of such contaminations. As an example, Hajj is a world wide ceremony that can affect every country with Muslim sub-population regarding surge of multi-microbial and drug resistant respiratory tract infections. Therefore disease prevention in the involved societies would be highly life and cost saving. Besides use of common antibiotics that has major drawbacks, natural immune boosters are viable and accredited options in this field. Echinacea supplements are well-known for immune-modulation and anti-flu effects. They have all characteristics that recommended by CDC to fight flu: immune augmentation, evidence-based preventive value and anti-viral (microbial) properties without promoting any resistance or life-threatening adverse reactions. Echinacea vastly grows in different geographical teritories, is reasonably affordable and easily accessible almost all over the world just like in Iran. As we published in a recent review article, there is a huge amount of evidence that shows promising results for Echinacea in both prevention and treatment of respiratory tract infections especially in high risk populations and would be potentially useful in susceptible travelers. There will be a great opportunity to prevent respiratory tract infections related to international gatherings and their infectious adverse consequenses with standard protocls for supplementation of natural products like Echinacea after adequate examinations via goal-directed clinical trials.
Anil kumar Prasad
Indian Virological Society, India
Title: Influenza prevention essential in developing countries
Biography:
Anil kumar Prasad is the currently working as President of Indian Virological Society.He is also the chairman of Influenza Foundation of India.He was elected Fellow of the Geriatric Society of India (FGSI) 2014 at their Nagpur Convention (8-9 November, 2014).He has also Published over 60 Research Papers in national & International Journals & 3 Books (Chapter on Influenza).He has also received Life Time Achievement Award conferred by the Geriatric Society of India on 06th November, 2014 at the Vaccine Advocacy for the S E Asian Countries held at Delhi.
Abstract:
TBA
Chiek J. Er
Norwegian Veterinary Institute, Norway
Title: Occurrence and spread of influenza A(H1N1)pdm09 virus infection in Norwegian pig herds based on active serosurveillance from 2010 to 2014
Biography:
Chiek Er has been a veterinary epdidemiologist with the Norwegian Veterinary Institute since 2007. His current research activities focus on the epidemiological aspects of influenza A(H1N1)pdm09. Since 2009, he has coauthored 7 published articles on influenza A(H1N1)pdm09. He is first author for the three latest ones.
Abstract:
The incursion of influenza A(H1N1)pdm09 virus was detected by Norway’s active serosurveillance of its pig population in 2009. Since then, surveillance data from 2010 to 2014 revealed that 54% of 5643 herd tests involving 1567 pig herds and 28% of 23 036 blood samples screened positive for antibodies against influenza A virus. Positive herds were confirmed to have influenza A(H1N1)pdm09 virus infection by haemagglutination inhibition test. In 50% of positive herd tests, 560% of the sampled pigs in each herd had antibodies against influenza A(H1N1) pdm09 virus. This within-herd animal seroprevalence did not vary for type of production, herd size or year of test. The overall running mean of national herd seroprevalence, and annual herd incidence risks fluctuated narrowly around the means of 45% and 32%, respectively, with the highest levels recorded in the three densest pig-producing counties. The probability of a herd being seropositive varied in the five production classes, which were sow pools, multiplier herds, conventional sow herds, nucleus herds, and fattening herds in descending order of likelihood. Large herds were more likely to be seropositive. Seropositive herds were highly likely to be seropositive the following year. The study shows that influenza A(H1N1)pdm09 virus is established in the Norwegian pig population with recurrent and new herd infections every year with the national herd seroprevalence in 2014 hovering at around 43% (95% confidence interval (40–46%).
Hany Khalil
University of Sadat City, Egypt
Title: Novel and efficacious compounds disturb influenza A virus infection
Biography:
Hany Khalil has completed his PhD at the age of 35 years from Humboldt University in collaboration with Max-Planck Institute for Infection Biology followed by 6 months postdoctoral fellowship at Max-Planck Institute for Infection Biology, Berlin, Germany . Additional 4 months postdoctoral fellowship at Wexner Medical Research Center, Ohio State University, USA. He is the Assistant Professor at Genetic Engineering and Biotechnology Research Institute, Department of Molecular Biology, University of Sadat City Egypt. He is Principle Investigator in Two different projects supported by (STDF) projects ID,6117 and project ID, 4694.
Abstract:
Influenza A virus is a negative RNA stranded virus of the family Orthomyxoviridae, and represents a major public health threat, compounding existing disease conditions. Influenza A virus replicates rapidly within its host and the segmented nature of its genome facilitates re-assortment, whereby whole genes are exchanged between influenza virus subtypes during replication. Antiviral medications are important pharmacological tools in influenza virus prophylaxis and therapy. However, the use of currently available antiviral is impeded by sometimes high levels of resistance in circulating virus strains. Notably, the over use of existing antiviral drugs such as oseltamivir (Tamiflu) and zanamavir (Relenza) increases the likelihood of viral escape mutations. Here, we identified novel anti-influenza compounds through screening of chemical compounds that synthesized de novo and several naturally occurring products on human lung epithelial cells. Computational and experimental screening of extensive natural products and water soluble chemical compounds identified novel influenza virus inhibitors that can reduce influenza virus infection without any detectable toxic effects on host cells. Interestingly, the indicated active chemical compounds inhibit viral replication most likely via interaction with cell receptors and disturb influenza virus entry into host cells. Additionally, the selected natural product inhabits viral replication via increasing of interferon beta (IFN-β) production from infected cells. In conclusion, screening of new synthesis compounds and natural extractions on influenza A virus replication provides a novel and efficacious anti-influenza compounds that can inhibit viral replication and indicates that these compounds are attractive candidates for evaluation as a potential anti-influenza.
Jehan El Kholy
Cairo University Hospital, Egypt
Title: Burden of acute lower respiratory tract infection caused by influenza virus among children in Egypt
Biography:
Jehan El Kholy is a Professor of Anesthesia and Intensive Care who works as a Deputy Director of Cairo University Hospitals since 2013. She is a certified Infection Prevention and Control Specialist and she is responsible for preparedness and response to influenza and other infections in a teaching hospital that plays a role model among all Egyptian hospitals in collaboration with Naval Medical Research Unit, No.3 (NAMRU-3). She was awarded by the Egyptian Minister of Health to be the Best Leader Implementing Active Surveillance of Influenza and healthcare- associated infections in Cairo University Hospitals.
Abstract:
Background: Influenza virus is one of the most important causes of acute lower respiratory tract infections (ALRTI) in children. We aimed to assess the burden of influenza among hospitalized children less than 5 years in Egypt. Methods: We enrolled 3075 patients, of which 77.8% were children less than 5 years old diagnosed with ALRTI admitted to Cairo University Hospitals during five-year period from 2010 to 2014. Nasopharyngeal aspirates were obtained from the patients and tested for influenza among 16 respiratory viruses by mutliplex PCR. Results: Patients had a mean age of 4 months, 53.4% were males. Average hospitalization duration was 5 days, 35% were positive for one or more virus. Influenza A and influenza B were detected in 6.2% and 3.2% of children respectively. All influenza patients presented with cough and fever. More than 80% had tachypnea and nasal flare. Complications were associated with chronic lung and heart conditions. The most common complications were ARDS (81.8%), requiring ICU admission (12%) and death in 8.2%; though seasonal distribution was not consistent, yet 80% of influenza cases occurred in winter and early spring seasons (p<0.001). Nosocomial transmission occurred in 2 outbreaks in a Surgical Pediatric Intensive care units, affecting 7 children. Conclusion: Influenza is an important etiology of ALRTI in children below 5 years of age. As it is more prevalent in winter and tends to cause severe infection in high risk group, vaccination, rapid diagnosis and early start of antiviral therapy are essential.
Melia Magnen
Institut National de la Santé et de la Recherche Médicale, France
Title: Kallikrein-related peptidase 5 contributes to H3N2 influenza virus infection in human lungs
Biography:
Melia Magnen is currentlypersuing her PhD at the CEPR, Tours, France.
Abstract:
The cleavage of the influenza A virus hemagglutinin (HA) by host serine-proteases is essential for viral infectivity. Several serine proteases of the kallikrein-related peptidase (KLK) family are produced and secreted by the airways and we investigated whether KLK1, 5 and 14 were involved in seasonal IAV infection. Expression of KLK1, 5 and 14 was assessed at the protein levels, in human tracheal aspirates from flu patients in intensive care unit, using ELISA. Primary human bronchial epithelial cells (hBEC) cultured at the Air-liquid interface were infected with IAV and the expression of KLKs was analyzed by RT-qPCR and flow cytometry. We also investigated in vitro if KLK1, 5 and 14 were able to cleave HA precursors. Finally, inactivated virions (mouse adapted A/Scotland20/74, H3N2) were treated with KLKs and the infectiveness was determined in MDCK cells and in mice. Flu infection selectively increased expression of KLK5 in hBEC and its secretion in the human airways. KLK1, 5 and 14 were able to cleave in vitro HA precursor from several subtypes of influenza viruses. Furthermore, only the KLK5 treatment of H3N2 virions promoted IAV infection in MDCK cells. In mice, the treated virus led to severe infection with KLK5 treatment and to moderate one with KLK14 treatment. KLK1 virus treatment did not result in infection. Expression and secretion of KLK5 is specifically induced in airways upon flu. This induction likely contributes to the propagation of the virus in favoring its multi-cycle replication through activation of the HA precursor.