Day 2 :
Keynote Forum
Kei Numazaki
International University of Health and Welfare, Japan
Keynote: Development of rapid diagnostic reagents for respiratory viral and mycoplasmal infections in children
Time : 09:00-09:45
Biography:
KEI, NUMAZAKI Physician & Microbiologist; MD, Sapporo Med, 1980, PhD, 1985.Med. diplomate. Staff Pediatrician Hokkaido Children’s Hospital, 1985-1986; Postdoctoral Fellow McGill Montreal, Can, 1986-1989, Adjunct Prof, 1994-2004;Sr. Lectr. Sapporo Med. U,1990-1993, Asst. Prof,1993-2004, Head of Regional Reference Laboratory and Global Specialized Laboratory, WHO, 2005-2008; 2008- till date Professor & Chair, Division of International Infectious Diseases, Graduate School, Departments of Pediatrics, University Hospital, International University of Health and Welfare, Tochigi, Japan.
Abstract:
Establishment of rapid diagnosis of respiratory virus infections in children is important not only from the standpoint of clinical diagnosis but also infection control. We have developed and reported about the fundamental results of a rapid diagnostic reagent for measles that employs the lateral flow-based immuno-chromatography. The purpose of the present study is to investigate the possibility of diagnosing with rapid diagnostic reagents for viral and mycoplasmal antigens of respiratory tract. To investigate the etiology of pediatric community acquired respiratory infections, we conducted a prospective, population based study covering the total population less than 15 years of age in Nasu-shiobara, Tochigi, Japan, during the period of December 2010 to March 2013. Nasopharyngeal swabs were collected from 200 children with respiratory tract infections. RT-PCR analysis was used as the reference assay. Results are expressed as the equivalent of copies per micro-liter according to titration of control RNA. The correlation of the results between obtained by the diagnostic reagents and RT-PCR assays was investigated. Specific infecting agents were identified in a total of 64 (32.0%) out of 200 patients with mixed infection as follows: Respiratory syncytial (RS) virus, 29; Mycoplasma pneumoniae, 17; metapneumovirus, 7; adenovirus, 5; influenza A virus, 3; and influenza B virus, 3. We detected 100 copies in the sample/μl or more antigens of Mycoplasma pneumoniae and metapneumoviruswhich were difficult for detection by the conventional method. Minimum detection sensitivity of the reagent system in the clinical material was the 3×101 copies/micro-liter. The correlation of the results between obtained by the diagnostic reagents and RT-PCR was the positive results that match rates of 79.0 to 100% and 100% negative match. From the results of this study the importance of M. pneumoniae and RS virus in the etiology of lower respiratory infections in Japanese children was confirmed. Immuno-chromatography can be applied as a simple rapid diagnostic method from the beginning of the disease in general clinical practice.
Keynote Forum
Michele Stone
University of Maryland, USA
Keynote: Title: Changing the Paradigm of Vaccine Devlopment and Production
Time : 09:45-10:30
Biography:
Michele Stone has completed her PhD in Biochemistry and Molecular Biology from University of Maryland, Baltimore and Postdoctoral studies also at the University of Maryland in the fields of Physiology and Neuorscience. She is currently the Executive Director of Vaccines at Liquidia Technologies, a premier biotechnology company focused on development of particulate based drug products to provide global health solutions. She has published more than 15 patents and many articles in reputed journals. She has a PMP certification and brings a perspective of life cycle management to product development.
Abstract:
The future of vaccine development will integrate quality by design at vaccine conception to ensure desired efficacy and safety product profiles. The ability to define protective immune responses and desired mechanisms to target appropriate immune cells would be a key advantage in the development of next generation vaccines. For respiratory diseases like Flu and Pneumonia, protection from disease is generated by antibodies recognizing surface antigens. Intracellular pathogens like Mycobacterium tuberculosisrequire more sophisticated immunological responses to both control and eliminate disease. The evolution of vaccine development has evolved from inactivated whole cell microorganisms, to subunit vaccines that contain protein or protein-PS conjugates, to next generation vaccine candidates that include completely synthetic systems. Novel technologies allowing developers to design vaccines targeting specific immune response via selection of protective antigens with or without adjuvants would enable more directed immune targeting and potentially provide increased efficacy with improved safety outcomes. The PRINT® technology is a novel particle platform technology designed to incorporate quality early in the development process. The PRINT technology enables unique formulation advantages that have broad implications to vaccines development and production methodologies. The induction of potent immune responses to multiple protein/polysaccharide antigens without adjuvants has been demonstrated with PRINT particles. Co-delivery of antigens and adjuvants has been shown to improve both T cell and B cell immune responses including adjuvant dose sparing. Formulation of combination vaccine products containing incompatible components has also been shown with PRINT particles. The advantages demonstrated to date by the PRINT technology could profoundly impact the vaccine industry as products are brought to the clinic.
- H1N1 Influenza Virus -Immunology and Genetics Features | Ebola, Arboviral dieases and Haemorrhagic Fever | Vaccines against Infectious & Non-infectious diseases
Chair
Jorge Alberto Panameno Pineda
Fundacion Salvadorena para la Inmunoinfectologia y Medicina Tropical, USA
Session Introduction
Valery A Petrenko
Auburn University, USA
Title: Title: Discovery of host cell-binding sites in the hemagglutinin of influenza virus using polyvalent (‘landscape’) peptide phage-displayed library as a molecular adaptation system
Biography:
Valery A Petrenko is currently a Professor in Auburn University, USA. He was graduated from Moscow State University (1972), received PhD and DSc degrees from the Institute of Organic Chemistry (1976) and Moscow State University (1988) and has ranks of Senior Scientist (1984) and Professor in Bioorganic Chemistry and Molecular Biology (1992) from the Government of the USSR. He has served as a Senior Scientist (1977-1982), Laboratory Head (1982-1985), Associate Director of Research, Institute Director (1985-1989), Vice President of Research and Professor (1989-1993) in the Association “Vector” (Novosibirsk, Russia). In 1993, he has joined the faculty of University of Missouri, Columbia as a Visiting and Research Professor and in 2000 the faculty of Auburn University as Professor. He is the recipient (PI) of grants from the ARO, NIH-NCI, Calvert Research, LLC and AURIC. He is also a Member of National Academy of Inventors Chapter (2013), Auburn University Research Initiative in Cancer (AURIC), National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer (2009) and Phi Zeta Honor Society of Veterinary Medicine. His research interests include monitoring and detection of biological threats, diagnosis of infectious and cancer diseases and tumor targeting.
Abstract:
During natural evolution, viruses have evolved into molecular structures with optimized relationships with a host. In particular, viruses acquired surface peptides that allow them to attach to a host cells and invade into the cells through interaction with cellular receptors and co-receptors. Identification of these cell-recognition peptides would offer a strong basis for development of antiviral drugs, vaccines and diagnostics, prediction of viral drifts from one host to another and prediction and control of emergent infections. Bacteriophage Fd possesses no natural tropism to mammalian cells and is suitable as a vector for generating random peptide phage-displayed libraries. It was shown that phages selected from these libraries are able to specifically recognize cellular receptors and penetrate into sub-cellular compartments during their artificial molecular evolution in vitro, similarly to evolution observed with naturally evolved viruses. We hypothesized that selection of cell-associated phage variants from their multi-billion clone libraries and bioinformatic analysis of their cell-binding peptides in comparison with proteins of natural viruses would allow the elucidation of functional virus-host binding sites used during viral pathogenesis. To test our hypothesis, we enriched a subpopulation of phages that interact with human small airway epithelial (SAE) cells and identified the recovered sequences by next-generation sequencing. We then analyzed the phage sequence library against consensus sequences of representative viral proteins, such as hemagglutinin (HA) from different influenza strains over the past 6 years and 5 of the last major pandemics. Several families of peptides were identified with high structural homology to some previously recognized functional segments of HA in the mature viral particles. The identified regions were associated primarily with the membrane fusion peptide domain and the HA0 cleavage site. However other regions were identified suggesting identification of residues involved with a potential co-receptor binding site (CoRBS). The identified peptides revealed regions of HA that were not previously identified as a receptor binding site (RBS) or common antigenic region. Our findings justify the hypothesis that similar mechanisms of molecular adaptation are used in viruses to adjust HA proteins to mammalian cell receptors. After testing their immunological activity, the identified phage peptides can be used as lead compounds for construction of molecular and phage-based vaccines to protect the host from the corresponding virus.
Antonio Mastroianni
Unità Operativa Malattie Infettive, Italy
Title: Title: Dengue and plasmodium falciparum malaria confection. imported cases in tralevers and a review of the literature
Biography:
Antonio Mastroianni, M.D,Jul 1996—-present, is currently working as a medical physician specialist in Infectious Diseases & Tropical Diseases with a “high degree in antibiotic and antifungal treatment” at Presidio Ospedaliero “G.B. Morgagni – L. Pierantoni”, Dipartimento di Medicina Specialistica, Unità Operativa Malattie Infettive, Forlì, Italy
Abstract:
Malaria and dengue (DENV) are both common in the tropical countries in geographical areas where both the vectors (Anopheles mosquito and Aedesmosquito, respectively) coexist. Simultaneous infections in areas where both diseases are co-endemic in many places of the world are possible, although under-recognized and not frequently reported. The aim of this report is to describe two imported cases of dual infection with falciparum malaria and DENV in a 20-year-old Italian girl and in a 13-years old Jessica after returning from Burkina Faso, the first case series of imported DENV and falciparum malaria co-infection in Italy. We emphasize the need for increased surveillance of the possible malaria and DENV co-infection in travelers after returning in Europe from endemic areas. Diagnostic assessment of imported fever should rely mainly on geographic exposure, on specific risk profiles and clinical parameters. Differential diagnosis may be particularly critical and early diagnosis of the main tropical conditions would further improve patient management. Malaria and DENV have similar clinical findings but the treatment of these two illnesses is different and consequently diagnosis of one should not rule out testing for the other infection. A literature search suggest that dual infections are not uncommon and it would have different implications for clinicians, including unexpected clinical and laboratory findings. Clinicians should maintaining a high level of clinical suspicion against both malaria and dengue and the possibility of co-infection in the evaluation of international travelers returning in a European country from endemic areas usually in the tropics.
A M Balde
Gamal Abdel Nasser University of Conakry, Guinea
Title: Title: Ethnomedical and ethnobotanical investigations on the response capacities of guinean traditional health practioners in the management of outbreaks of infectious diseases: The case of the ebola virus epide
Biography:
My academic evolution was realized at the Faculty of Pharmacy of the University of Conakry, Guinea (1968-1973; PharmD in 1973), the Institute of Pharmacy (Free University of Brussels, Belgium ;1983-1986), the Tropical Medicine Institute of Antwerp, Belgium (1985-1987), the Department of Pharmaceutical Sciences, University of Antwerp, Belgium (1986-1991; PhD in 1990). I’ve been the chief of the department of pharmacy (University of Conakry) from 1998 to 2010 and I’m the General Manager of the Research and Valorization Center on Medicinal Plants (Dubreka) since 2000. As a full professor, I’m teaching pharmacognosy, ethnopharmacology and phytochemistry to students of pharmacy, biology and chemistry in the Guinean universities.
Abstract:
Like many other emerging diseases, the recent Ebola outbreak in West Africa illustrated the crucial role of the ecological, social, political and economic context within which diseases emerge. In the infected areas, the threat of Ebola has limited the ability of local health-care systems to provide standard care, leaving people with Ebola or non-Ebola Virus Disease-related health disorders without necessary care. Moreover, the mistrust towards the official authorities along with the fear of the disease prevents a number of patients to consult the conventional health care centers. Consequently, millions of Guinean people remained at risk of contamination. For these, traditional medicine has been continued to be the first and most important source of medicinal solace when illness strikes health. While international efforts focus on new vaccines, medicines and diagnostics, no coherent national or international approach exists to integrate the potential of the traditional health practitioners (THPs) in the management of infectious diseases epidemics. In spite of its social importance, traditional medicine continues to be largely disregarded in health development planning. An ethnomedical survey conducted in the 4 main Guinean regions led to the contacts of a total of 113 traditional health practioners and the collection of 54 plant species from which 44 identified belonging to 26 families. The traditional treatment of the main symptoms was based on 47 vegetal recipes which were focused on the treatment of diarrhea (22 recipes), fever (22 recipes), vomiting (2 recipes), external antiseptic (2 recipes), hemorrhagic syndrome (2 recipes), convulsion and dysentery (one recipe each). Literature data on the 12 most cited plant species tends to corroborate their traditional use and to highlight their pharmacological potential. Upon the above considerations and taking into account traditional health practitioners have always played a central role in the medical management of their community and tend to be the entry point for care in many African communities, particularly in remote rural areas, it is worth to document all available knowledge on the traditional management of EVD-like symptoms in order to evaluate systematically the anti-Ebola potential of Guinean plant species.
Biography:
James W. Gillespie graduated from Auburn University with a BS in Biochemistry (2007) and completed a Ph.D. in Biomedical Sciences (2015). In 2016, he joined the faculty of the College of Veterinary Medicine at Auburn University as a Research Assistant Professor. He has served as Key Personnel and Co-PI on grants from the NIH-NCI and AURIC. He is a member of the American Association of Pharmaceutical Scientists (AAPS), American Chemical Society (ACS), Auburn University Research Initiative in Cancer (AURIC), and the National Cancer Institute Alliance for Nanotechnology in Cancer (2009-2015). His current research interests include phage display, development of precision nanomedicines, and prevention/diagnosis/treatment of neoplastic and infectious deceases.
Abstract:
Viruses lack the ability to replicate without a host. Therefore, to ensure replication and continued persistence in an environment they must acquire mutations in their capsid proteins, through natural selection, to allow specific interactions with receptors expressed on a host cell. These interaction sites are ideal targets for vaccine development or therapeutic drug development, but identification can be time consuming or highly variable due to antigenic drift and rapid mutation rates of the virus. The filamentous bacteriophage, fd, has no natural tissue tropism to mammalian cells, but can be engineered to display short peptides fused to the 4,000 copies of its major coat protein. We hypothesize that these engineered phages can be used to predict interaction sites of natural viruses with a host. Here, we enriched for a sublibrary of phage clones that interact with small airway epithelial (SAE) cells from a multi-billion phage library and identified the recovered sequences by next-generation sequencing (NGS). Representative consensus sequences for influenza hemagglutinin (HA) and neuraminidase (NA) proteins were generated using the NCBI Influenza Virus Resource. Using blastp with settings optimized for short peptides, the resulting sequences were searched against our recovered phage sublibrary interacting with SAE cells. Several peptides with high structural homology to either influenza structural proteins were identified. The recovered peptides were found near previously identified functional domains including, the membrane fusion domain and the HA0 cleavage site of HA. Additional domains were identified suggesting residues that may be involved with a co-receptor binding site. Here, we justify the use of phage display as an artificial evolution system in combination with next generation sequencing datasets to identify virus-host interaction sites based on the protein sequence of the virus. This technique can be extended to broader applications to rapidly identify interaction sites of novel pandemic or high-risk viral pathogens.
Merita Kucuku
National Agency for Medicines & Medical Devices, Albania
Title: Title: The safety of yellow fever vaccine, international experience for different cases
Biography:
Merita Kucuku is currently working in National Agency for Medicines and Medical Devices of Albania for safety, control and efficacy of vaccines. She was the Head of National Regulatory Authority of Vaccines & Immunobiological Products of Albania from 2006-2012. She has completed her MSc in 2006 and PhD on University of Tirana in Faculty of Natural Science Tirana Albania in 2010. She is a Member of Abortion WG for safety of the Global Alignment of Immunization Safety in Pregnancy (GAIA Project), Member of working group for case definiton-vasculitis, arranged from AIFA-Italy & Brighton Collaboration Geneva Switzerland and Member of reference group for the first five neonatal & first five obstetric case definitions related to immunization in pregnancy.
Abstract:
Yellow fever virus is from family flaviviridae and is endemic in African countries and Latin America. Over 900 million people are living in endemic area and are risked from infection of yellow fever. Illness ranges in severity from a self-limited febrile illness to severe liver disease with bleeding and is diagnosed based on symptoms, physical findings, laboratory testing and travel history, including the possibility of exposure to infected mosquitoes. There is no specific treatment for yellow fever; care is based on symptoms. The steps necessary to prevent yellow fever virus infection includes using insect repellent, wearing protective clothing and getting vaccinated. Yellow fever vaccine is recommended for endemic countries and over 500 million people are vaccinated with yellow fever vaccine 17D. The countries which are not endemic are recommended to vaccinate people in cases of travelling in endemic areas to avoid the importation of yellow fever virus and epidemic outbreak in country. The cases of yellow fever are reported in countries free of yellow. According the data based on the different studies in different countries the Yellow Fever 17D and 17DD is very safe vaccines and effective against illness and the best way for preventing yellow fever infection.
Michele Stone
University of Maryland, USA
Title: Title: Enhancing antigen delivery and immunogenicity through the use of particles in vaccines
Biography:
Michele Stone has completed her PhD in Biochemistry and Molecular Biology from University of Maryland, Baltimore and Postdoctoral studies also at the University of Maryland in the fields of Physiology and Neuorscience. She is currently the Executive Director of Vaccines at Liquidia Technologies, a premier biotechnology company focused on development of particulate based drug products to provide global health solutions. She has published more than 15 patents and many articles in reputed journals. She has a PMP certification and brings a perspective of life cycle management to product development.
Abstract:
The future of vaccine development will integrate quality by design at vaccine conception to ensure desired efficacy and safety product profiles. The ability to define protective immune responses and desired mechanisms to target appropriate immune cells would be a key advantage in the development of next generation vaccines. For respiratory diseases like Flu and Pneumonia, protection from disease is generated by antibodies recognizing surface antigens. Intracellular pathogens like Mycobacterium tuberculosisrequire more sophisticated immunological responses to both control and eliminate disease. The evolution of vaccine development has evolved from inactivated whole cell microorganisms, to subunit vaccines that contain protein or protein-PS conjugates, to next generation vaccine candidates that include completely synthetic systems. Novel technologies allowing developers to design vaccines targeting specific immune response via selection of protective antigens with or without adjuvants would enable more directed immune targeting and potentially provide increased efficacy with improved safety outcomes. The PRINT® technology is a novel particle platform technology designed to incorporate quality early in the development process. The PRINT technology enables unique formulation advantages that have broad implications to vaccines development and production methodologies. The induction of potent immune responses to multiple protein/polysaccharide antigens without adjuvants has been demonstrated with PRINT particles. Co-delivery of antigens and adjuvants has been shown to improve both T cell and B cell immune responses including adjuvant dose sparing. Formulation of combination vaccine products containing incompatible components has also been shown with PRINT particles. The advantages demonstrated to date by the PRINT technology could profoundly impact the vaccine industry as products are brought to the clinic.