4^th International Conference on Influenza and Zoonotic Diseases July 02-04, 2018 Vienna, Austria

Biography:

Petr Maly is head of Laboratory of Ligand Engineering at the Institute of Biotechnology, Czech Academy of Sciences in Vestec, Czech Republic. He studied at Department of Biochemistry, Faculty of Science, Charles University in Prague, Czech Republic(1980-1985) and completed doctorate at the Institute of Molecular Genetics ASCR (IMG) in Prague. He spent postdoctoral fellowship (1992-1995) at Department of Pathology and Howard Hughes Medical Institute, The University of Michigan Medical School, Ann Arbor, USA, in the laboratory of Prof. John B. Lowe where he published several substantial papers related to in vivorole of mammalian glycosyltransferases. Since 1998 to 2005 he was a research group leader at the IMG in Prague. As a visiting scientist he also worked at Department of Biochemistry and Molecular Biology, College of Medicine, University of Oklahoma, USA. He also was participating investigator of Consortium for Functional Glycomics (USA, 2001–2008) and Member of Editorial Board (2001-2005) and Editor (since 2003) of the Czech journal “Biologicke listy” (Biological Letters). Since 2008, he has been working on the development of combinatorial protein libraries derived from small protein scaffolds andconstruction of novel high-affinity protein binders with therapeutic and diagnostic potential.

Abstract:

Carbohydrates-based immunogens are generally less effective in generation of long-lasting antibody responses and neutralizing epitopes of surface glycoproteins are poorly immunogenic. Therefore, proteins mimicking glycan epitopes represent a promising alternative for development of more protective vaccines. Highly complex combinatorial libraries derived from scaffolds of small and robust protein domains represent an excellent tool for the identification of protein binders mimicking surface glycopeptide epitopes of viruses or bacteria that are recognized by broadly neutralizing antibodies. We use our established concept of a highly complex combinatorial library derived from scaffold of 46 amino acid albumin-binding domain (ABD) and, in combination with ribosome display, we target broadly neutralizing(bn) IgG to identify unique binding candidates recognizing antigen-binding-domain of the tested bn-IgG. In our proof-of-concept study we target glycan epitopes carried by gp120/gp41 protein complex of the HIV-1 Env.ABD variants as potential (glyco)peptide mimetics are currently being characterized for the stimulation of HIV-1 gp120-specific neutralizing antibody response. Thus, ABD-derived recombinant mimotopes could serve as a useful molecular clue for generation of more efficient HIV-1 vaccine and provide a platform for development of other viral or bacterial disease-preventing vaccines.

The project was supported by Czech Ministry of Health grant AZV MZ 15-32198A and Czech Ministry of Education, Youth, and Sport grant CEREBIT CZ.02.1.01/0.0/0.0/16_025/0007397.

Biography:

Dr Annete Vogel is presently the Head of Infectious Disease Vaccines, BioNTech AG, Germany. She has been associated with Friedrich-Loeffler-Institut, Federal Reserch Institute for Animal Health as scientist. She has done her education from Georg-August-University Goettingen and completed her DSc from Eberhard-Karls-University Tubingen. She has many publications to her name like “PAR1 contributes to influenza A virus pathogenicity in mice”, “Influenza virus infection aggravates stroke outcome” to name a few. Her Research interest spans around cell culture, animal models, infectious disease, flow cytometry, virology, vaccination, serology and genomics.

Abstract:

Vaccines are the most effective method of controlling infectious diseases. However, todays vaccine production is facing difficult challenges, as the concepts are often not fast and flexible enough to allow quick responses for the efficient control and prevention of global outbreaks of newly emerging and re-emerging viruses and the adaption to new antigenic drifts.

To address this challenge, BioNTech RNA Pharmaceuticals GmbH is developing an innovative synthetic Amplified Immune Response (A.I.R) vaccine platform against Infectious Diseases that is characterized by short manufacturing times, high flexibility and the feasible production of at least 100,000 RNA-based human vaccination doses per week based on the low concentration needed. The administration of in vitro transcribed self-amplifying RNA (saRNA) results in higher antigen expression than delivery of comparable amounts of mRNA, correlating rather to the final subgenomic transcript copy number than to initially transferred RNA amounts. However, antigen expression is still transient as innate immunity effectively prevents persistent replication. Against influenza virus, both B and T cell-responses are induced. We were able to show high antibody titres in mice for over a one year period and protection against live viral challenge after prime-boost as well as after single vaccination by using submicrogram quantities of saRNA. In summary, A.I.R vaccines give equivalent protection against Influenza to mRNA vaccines but at much lower doses.

Biography:

Prokopyeva Elena has completed her PhD at the age of 29 years from FBRI State Research Center of Virology and Biotechnology ‘Vector’(Koltsovo, Russia). Dissertation title: «Phenotypic and genotypic properties of pandemic influenza A(H1N1)pdm09 virus during adaptation to mice of different genotypes». She conduct postdoctoral studies from Novosibirsk State University and Research Center of Experimental and Clinical Medicine (Novosibirsk, Russia). She is the researcher of the Laboratory experimental simulation and pathogenesis of infectious diseases, and the teacher of the course “Embryology” and “ General Histology” at Novosibirsk State University (NSU). She has published more than 25 papers in reputed journals. She has been conducting supervision of undergraduates at NSU since 2016. Also Prokopyeva Elena has obtained different honors and awards in the field of Virology, Pathology and Medical Microbiology.

Abstract:

Pandemic A (H1N1) pdm09 virus has caused substantial morbidity and mortality globally and continues to circulate, which may lead to an increase the pathogenic features of viruses by adaptation to the human. To address this problem, we studied changes of biological properties of the pandemic viruses during adaptation to experimental mammals and analyzed cellular localization of positive-stranded A(H1N1)pdm09 RNA in the inner organs of infected mice. To increase the virulence of pandemic H1N1 isolates in mice, we produced mouse-adapted variants of A(H1N1)pdm09 strain by serial lung-to- lung passages in BALB/c mice. After total of 7 passages we got the lethal strains to BALB/c mice (BALB/c-MA) with meaning of 50% lethal dose 1,2 lgTCID50/ml. Hematoxylin-eosin staining, immunohistochemistry for type A influenza nucleoprotein antigen, and real-time reverse transcription-PCR assay for viral RNA were performed. Complete genome sequences of the wild-type and mouse-adapted A (H1N1)pdm09 influenza viruses revealed 19 amino acid substitutions in different viral proteins (HA, NA, NS2, NS1, PB2, PB1, NP). In lung tissue under the influence of not adapted and mouse-adapted variants of A(H1N1)pdm09 influenza viruses developed interstitial pneumonitis, but it is noted the greatest degree of inflammation in case of infection of the strain BALB/c-MA. Comparative analysis revealed accumulation of viral titers in the brain (3,75±0,22 lgTCID50/ml), liver (2,5±0,5 lgTCID50/ml) and the kidney (0,74±0,48 lgTCID50/ml) in case of infection only of the strain BALB/c-MA. Immunohistochemistry staining of viral antigens was demonstrated in the lung pneumocytes and mucous glands under influence of both wild-type and mouse-adapted viruses. But only in case of infection with BALB/c-MA immunostaining was detected also in the brain, liver, kidney and in the intestine. This study demonstrates cellular localization of positive-stranded A(H1N1)pdm09 RNA in the lungs, brain, liver, kidney and in the intestine that suggests viral replication of the mouse adapted variants of A(H1N1)pdm09 influenza virus in these tissues. The study was supported by a grant from the Russian Scientific Foundation (project No.17-44-07001).

Biography:

Henry Memczak studied nanotechnology at the University of Kassel, Germany and completed his PhD in biochemistry in 2014 at the University of Potsdam, Germany and the Fraunhofer Institute for Cell Therapy and Immunology, Germany. He has worked on the development of analytical biosensors for influenza detection and methods for peptide-based biointeraction analysis for several years, published several papers, holds two patents and co-founded the company qpa bioanalytics GmbH for the commercialization of novel peptide biochips. For his dedicated translational research he received several awards and scholarships.

Abstract:

The only cost-effective protection against influenza is vaccination. Due to rapid mutation continuously new subtypes appear, what requires annual reimmunization. For a correct vaccination recommendation, the circulating influenza strains have to be detected promptly and exactly and characterized regarding their antigenic properties. Due to recurring incidents of vaccine mismatches, there is a great need to speed up the process chain from identifying the right vaccine strains to their administration. The monitoring of subtypes as part of this process chain is carried out by national reference laboratories within the WHO Global Influenza Surveillance and Response System (GISRS). To this end, thousands of viruses from patient samples (e.g. throat smears) are isolated and analyzed each year. Currently this analysis involves complex and time-intensive (several weeks) animal experiments to produce specific hyperimmune sera in ferrets, which are necessary for the determination of the antigen profiles of circulating virus strains. These tests also bear difficulties in standardization and reproducibility, which restricts the significance of the results.

To replace this test a peptide-based assay for influenza virus subtyping is developed. The differentiation of the viruses takes place by a set of specifically designed peptidic recognition molecules which interact differently with the different influenza virus subtypes. The differentiation of influenza subtypes is performed by pattern recognition guided by machine learning algorithms, without any animal experiments.

Biography:

Dr. Slobodan Paessler, is a Professor in the Department of Pathology and Director of Galveston National Laboratory Preclinical Studies Core. Dr. Paessler is a co-principle investigator on the Universal Influenza Vaccine project funded by an NIAID grant at Etubics Corporation. He serves as the Director of Animal Biosafety Level 3 for the Institute of Human Infections and Immunity. He has been Member of Scientific Advisory Board at Etubics Corporation since July 2015. He serves as a Member of the Center for Biodefense & Emerging Infectious Diseases. He received a Dr. Med Vet (D.V.M) at Ludwig-Maximilian University and a Ph.D in Experimental Pathology from UTMB.

Abstract:

Flu epidemics and potential pandemics pose great challenges to public health institutions, scientists and vaccine producers. Creating right vaccine composition for different parts of the world is not trivial and has been historically very problematic. This often resulted in decrease in vaccinations and reduced trust in public health officials. To improve future protection of population against flu we urgently need new methods for vaccine efficacy prediction and vaccine virus selection. Recently, novel bioinformatics platform based on electronic biology was successfully utilized for real-time monitoring of influenza A viruses as well as for prediction of vaccine efficacy in Australia and USA in 2017 and 2018. Here we present wEB platform and its usage in identifying functional biological changes in haemagglutinin protein of influenza A viruses and how this knowledge can be applied for vaccine design, prediction of future vaccine efficacy and real-time virus evolution monitoring.

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:

The mechanics of flu related respiratory illness is not completely implicit as it includes; influenza, zoonotic and non-influenza pathogens. Precise diagnosis is difficult as it often mimics asthma out of control which has perplexed researchers for decades. This has led to treatment confusion and an underestimation that the primary cause of breathing difficulties is related to bronchiolitis-bronchiectasis. A microbiology respiratory viral panel (RVP) test via polymerase chain reaction (PCR) can identify whether there is a co-existing viral lung infection that may worsen the lung function. Viral flu-related respiratory infections are highly transmittable and may increase morbidity and mortality in patients with premorbid pulmonary disease and weakened immune systems. The symptoms of flu include dyspnea and coughing; after usual treatment with steroids and asthma medications, continue to have worsening symptoms causing re-hospitalization. Chest radiography for patients with respiratory distress due to flu are notable for; bronchial wall thickening, bronchiectasis and sub-segmental atelectasis, related air-flow obstruction. Rhinoviruses (RV) – enterovirus (EV) for example is under recognized as the leading cause of hospitalization for viral outbreaks. Respiratory Enterovirus is responsible for 10 to 15 million hospitalizations annually. Enterovirus (D-68) was attributed to 14 deaths in 2014 in the United States (USA) and 70 deaths in the 2011 Philippines D68 outbreak. Ever since the 2014 D68 outbreak, there has been a drastic increase in the number of patients hospitalized and re-hospitalized for flu symptoms associated with severe acute respiratory distress on the pediatric and oncology wards. Zoonotic agents such as coronavirus (HCoV) are passed bi-directionally between animals and humans and capable of joining with other viral agents. All this has created undefined burden on global clinical resources. More research is needed to understand the pathogenesis of viral bronchiolitis and bronchiectasis related respiratory illness to assist clinicians with recognition and treatment of this highly morbid disease.

Biography:

Christopher Chadwick is a Technical Officer in the Global Action Plan for Influenza Vaccines Secretariat at World Health Organization. Previously, he was a Global Health Officer in the office of Global Affairs at the US Department of Health and Human Services. He received a Master of Science degree in Public Health with a concentration in microbiology and emerging infectious diseases from Milken Institute School of Public Health at George Washington University and a Bachelor of Science in Microbiology from Louisiana State University.

Abstract:

Purpose: The World Health Organization’s Global Action Plan for Influenza Vaccine (GAP) was a 10-year initiative dedicated to reducing the global shortage and inequitable access to influenza vaccines in the event of an influenza pandemic. The overarching goal of the GAP was to develop the capacity to produce enough vaccines to immunize 70% of the global population with two doses of vaccines. The GAP aimed to achieve this goal by increasing evidence based seasonal influenza vaccine use; developing influenza vaccine production and regulatory capacity in 14 low and middle income countries (LMICs) and; encouraging the development of improved influenza vaccines.

Methods: Between 2006 and 2016, the WHO collaborated with member states and key stakeholders to address the global shortage of and increase equitable access to pandemic influenza vaccines in the event of an outbreak.

Results: The outcomes of the GAP include: A dramatic increase in countries with a seasonal influenza policy in place (115 member states by 2014 from a baseline of 74 in 2006); the development of 8 licensed pandemic influenza vaccines and 3 licensed seasonal influenza vaccines in 6 LMICs and; A global expansion of pandemic vaccine production capacity, especially in LMICs (potential global capacity of 6.4 billion doses estimated in 2015).

Discussion: Following the conclusion of the GAP in 2016, priorities for influenza vaccine preparedness moving forward are to sustain the production capacity of influenza manufacturers in LMICs, promote and stimulate innovative influenza vaccine research and development, identify root causes of influenza vaccine hesitancy, generate more evidence on vaccine effectiveness in specific risk groups, and identify innovative ways of addressing global pandemic influenza preparedness.