Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 4th World Congress on Virology San Antonio, USA.

Day 3 :

  • Track 10: Neurological Infections Associated with Viruses

Session Introduction

Sayed-Mahdi Marashi

Tehran University of Medical Sciences, Iran

Title: Efficient inhibition of HIV replication by targeting 3UTR transcripts using new modified miR-30a

Time : 09:30-09:50

Biography:

Academic Rank Assistant Professor 1. Ph.D Medical Virology, University College London, London, England, 2011 Thesis Title:Functional Competence of CD8+ T cell Responses specific to Cytomegalovirus in Common Variable Immunodeficiency. Supervisor:Professor Vince Emery 1. Avicenna Award for high Impact Factor (IF) article, The 15th Avicenna Festival, Tehran University of Medical Sciences, Tehran, Iran 4 Feb 2014, 2. PhD scholarship from Tehran University of Medical Sciences, Iran 2007-2011, 3. (Fellowship award for 4 months from University College London (UCL 2010 , 4. Travel grant for presentation in 14th Congress of Immunology in Japan 2010, 1. Board Member of Iranian Virology Association Iranian Virology Association, 2013-2016 2. Research Committee Member - Virology Department School of Public Health - Tehran University of Medical Sciences, 2013-Present 3. Assistant Professor of Virology School of Public Health - Tehran University of Medical Sciences, 2011-Present

Abstract:

RNA interference (RNAi) based gene therapy has currently been considered as a combinational anti-HIV-1 therapy. While artificial polycistronic microRNAs can reduce HIV-1 escape mutants, this approach causes cell toxicity by saturation of endogenous RNAi machinery. This study aimed to optimize the efficiency of RNAi gene therapy in order to reduce cell toxicity. We explored an artificial miR-30a-3´UTR (miR-3´UTR) from a single RNA pol II expressed transcript that targets simultaneously all viral transcripts. We constructed a pre-miR-30a backbones encoding siRNAthat targets the HIV-1 3´UTR. Our data indicated thatHIV-1 replication was significantly inhibited in the cell culture using miR-3´UTR construct, suggesting a promising tool for consideration of RNA-based gene therapy application.

Biography:

S. Mattar Ph.D, has research experience of 25 years on tropical infectious diseases He actuatlly is the director of Tropical Reserach Institute at University of Cordoba (http://web.www3.unicordoba.edu.co/es/iibt), He has published more than 100 papers in several peers journals. He is full professor of Microbiology and Immunology at University of Cordoba.

Abstract:

We conducted a cross-sectional descriptive study of cases compatible with viral encephalitis in three hospitals in the city of Monteria. We included 265 specimens of cerebrospinal fluid (CSF) of adults (n=118) and pediatric (n= 147) patients with clinically suspected of encephalitis. Cytochemical analysis and microbiological tests (Gram stain and culture) were performed; multiplex and nested PCR detection using 16 oligonucleotides for herpes simplex virus 1 and 2 (UL30 DNA polymerase) were done. The primers used were: Epstein Barr virus (gp71 DNA polymerase), Cytomegalovirus (UL54 DNA polymerase) and Varicella zoster virus (DNA polymerase). Herpesvirus DNA was detected in 57 (21.5%) samples, with the following distribution: 47 (17.7%) Herpes simplex virus 1 and 2, 7 (2.6%) Cytomegalovirus, 4 (1.5%) Varicella zoster virus and 2 (0.75%) Epstein Barr virus. Co-infection was seen in 3 patients, VZV+HSV1-2 (n=1) and CMV+HSV1-2 (n=2). A 52.6% (30/57) of adult patients shown viral DNA detection, the distribution was: HSV1-2 (n=22), CMV (n=4), VZV (n=1) and co-infections (VHS1-2+CMV ( n=2) , VHS1-2+VVZ (n=1). In a pediatric population 47.3% (27/57) DNA was identified with HSV1-2 (n=22), VZV (n=2), CMV (n=1), EBV (n=2). Three parameters of cytochemical analysis (glycorrhachia, proteinorhaquia and pleocytosis) were abnormal in 15.7% (9/57) of patients; 21% (12/57) of patients (adults n=11, pediatric n=1 ) were diagnosed with HIV. Patients sequelae were observed in 12.2% (7/57) and mortality was 10.5% (6/57). This is the first surveillance of herpes encephalitis conducted in Cordoba; the findings contribute to the epidemiology of encephalitis and clinical management of patients.

  • Track 11: Agriculture and Plant Virology

Session Introduction

Luine Rosele Renaud Vidal

Federal University of Paraná, Brazil

Title: Human enteroviruses and viral meningitis in southern, Brazil

Time : 09:50-10:10

Biography:

Abstract:

Neurotropic enteroviruses are important human pathogens of meningitis where approximately 90% of cases are due to echovirus and coxsackievirus. In Curitiba city, Brazil, approximately 50% of meningitis cases with hospitalization are attributed to viruses which are diagnosed mainly based on the differential cell count of cerebrospinal fluid (CSF). The aim of this study was to define the epidemiological profile and the molecular characterization of enterovirus (EV), in CSF samples collected from patients with signs and symptoms of viral meningitis. A total of 440 CSF samples were collected from patients in the period of July 2005 to June 2006. The samples were collected in suitable containers and sent refrigerated to the laboratory within 12 hours. CSF was selected according to the inclusion and exclusion criteria established for the study. The detection of the region 5'NCR of the EV genome was performed using reverse transcription followed by PCR (RT-PCR). In addition, the VP1 gene was amplified for further phylogenetic analysis. Cellular and biochemical characteristics of CSF, as well as, epidemiological characteristics were also analyzed. EV were detected in 49/440 (11%) of the samples by RT-PCR methodology. There was a predominance of positive samples in the age range of 7 to 14 years (41%) and 4 to 6 years (28.6%). A patient three months old presented mixed infection by EBV and EV. A higher circulation of the EV was observed during the summer months. By genomic sequencing the echovirus 30, echovirus 4 were detected and 5 samples were non typed human echovirus. A predominance of negative results (89%) in this study indicates that some factors limited the detection of viral genome in CSF samples. In conclusion the RT-PCR methodology permits the definition of the viral etiology in the central nervous system infections within 4-8 hours direct from CSF samples. It was detected echovirus types 30 and 4 and the majority of the samples presented negative results.

Biography:

Bhavin Bhatt is working as Research Scholar in Central University of Gujarat,India.

Abstract:

Abstract: Viral diseases on crop plants are major havoc for the reduction in the yield, both qualitatively and quantitatively. Geminiviridae constitute an important group of plant pathogens with genomes of ss DNA and is characterized by particle morphology of twinned incomplete icosahedra. Whitefly-transmitted geminiviruses (genus Begomovirus) infect variety of plants of economic importance including tomato, chilli, legumes, okra etc. in tropical and sub-tropical region. Hence, begomoviruses are greater menace in the agriculture due to new and resistant biotype of whitefly. French bean has established its importance in Indian horticulture due its exceptional nutritional value and also plays pivotal role in Indian Economy and sustainability of Indian agriculture. Amongst the various factors affecting yield and quality of the crop, viruses are becoming most potent threats tropically and sub tropically. Legume yellow mosaic viruses (LYMVs), responsible for yellow mosaic disease (YMD) in grain legumes, comprised of four different begomovirus species, viz.Mungbean Yellow mosaic India Virus, Horsegram yellow mosaic virus, Dolichos yellow mosaic virus and Mungbean Yellow mosaic Virus. Our aim was to assess diversity of begomoviral genome infecting to Phaseolus vulgaris L.We have cloned and characterizedbegomoviral genomic components associated with bean dwarf mosaic disease (BDMD) manifested leaf samples from Varanasi and Bangalore. Our results confirm that two distinct virus cause disease in French bean grown in geographically separated area. Host – pathogen interactions was studied by proteomic approach. The host proteins involved in defense, signal transduction and metabolism are modulated upon active virus infection. Overall, this study will throw a light on more integrative picture of the nature of BDMD. Understanding of molecular and functional aspects of viral infections will be beneficial in formulating better resistant strategies for viral disease management in French bean without compromising nutritional quality or yield.

  • Track 12: Animal Viruses
Biography:

Michel Pepin has completed his PhD at the age of 26 years from University of Lyon and postdoctoral studies from INRA and ANSES. He is now full professor of Microbiology/Immunology and Infectious Diseases at the National Veterinary School of Lyon (now VetAgroSup).

Abstract:

Norway rats (Rattus norvegicus) are prevalent in urban environments, and pose a threat to public health by serving as reservoirs for pathogens that can be transmitted to humans. To identify and assess the prevalence of zoonotic or not zoonotic viruses carried by rats, a next generation sequencing (NGS) method was developed following two steps ; the first one has been dedicated to get an efficient NGS method in order to improve the number of viral reads. For this pilot study, a rat lung sample positive for Seoul virus (SEOV) and previously detected by RT-PCR was used as positive control. SEOV is an hantavirus which can be transmitted to humans primarily via inhalation of aerosolized viruses from contaminated rat urine and faeces. Whilst infected reservoir hosts are asymptomatic, human infections can lead to hemorrhagic fever with renal syndrome (HFRS), with varying degrees of clinical severity. The results of this first study were twice and have permitted (i) to define a robust protocol for viral enrichment and (ii) to obtain the first complete sequence of SEOV detected in France. Phylogenetic analysis supports the inclusion of the Lyon SEOV within lineage 7 along with SEOV strains originating from SE Asia and the previously reported French & Belgian SEOV strains (Dupinay et al, Virol J, 2014). Following on from this pilot study, the virome of a larger number of commensal rats (n=10) has been determined using viral enrichment and NGS previously defined. Results of this second study (analysis in progress) will be presented and discussed.

Augustin Mouinga-Ondeme

International Center for Medical Research in Franceville, Gabon

Title: Simian foamy virus in non-human primates and cross-species transmission to humans in Gabon

Time : 12:45-13:05

Biography:

Abstract:

It is now known that all human retroviruses have a non-human primate counterpart. It has been reported that the presence of these retroviruses in humans is the result of interspecies transmission. Several authors have described the passage of a simian retrovirus, simian foamy virus (SFV), from primates to humans. To better understand this retroviral "zoonosis" in natural settings, we evaluated the presence of SFV in both captive and wild non-human primates and in humans at high risk, such as hunters and people bitten by a non-human primate, in Gabon, central Africa. A high prevalence of SFV was found in blood samples from non-human primates and in bush meat collected across the country. Mandrills were found to be highly infected with two distinct strains of SFV, depending on their geographical location. Furthermore, samples collected from hunters and non-human primate laboratory workers showed clear, extensive cross-species transmission of SFV. People who had been bitten by mandrills, gorillas and chimpanzees had persistent SFV infection with low genetic drift. Thus, SFV is presumed to be transmitted from non-human primates mainly through severe bites, involving contact between infected saliva and blood.

Julius Rajacani

Research Triangle Europe Research Center, Hungary

Title: Search for protective Epstein Barr virus (EBV) epitopes in rabbit model

Time : 14:05-14:25

Biography:

Abstract:

As recently reported, EBV infection in New Zealand white rabbits does not cause infectious mononucleosis (Rajčáni J. et.al., Intervirology 2014). The administration of high virus dose (108-109 EBV DNA copy per animal inoculated by naso-oral route) elicited a potent immune response when establishing latency dissimilar to that in humans. For the reliable assessment of IgG antibody response, we applied EA-D (early antigen p54) ELISA and immunoblot (IB) tests. The EBV DNA in peripheral white blood cells (WBC) and spleen was detected by classical and/or nested polymerase chain reactions (PCR) using LMP1 gene primers. In addition, the WBC smears were stained for LMP1 antigen by immunofluorescence (IF). The average positive infection rate in 21 rabbits as detected by IB at 2 different intervals post-infection (p.i.) has reached 69.2% if the antibodies were determined against Zta/BZLF1 antigen (transactivator protein), but was slightly lower (53.4%) when evaluated against the early p54 polypeptide antigen (DNA polymerase cofactor). We strongly believe that coincidence of p54 antibodies in the infected animals as detected by both, IB and EA-D ELISA, might reflect the replication of EBV in lymphatic and/or epithelium cells. No EBNA1 antibody was found in our EBV infected rabbits at any of the intervals tested (over 98 days p.i.); this possibly reflects the development of rare latency 0 in the rabbit model. In contrast to the frequency of serological response, viral DNA could be detected in WBCs and/or spleen of 7 out 21 infected rabbits only (30%). The PCR results were in good agreement with the LMP1 antigen expression. Immunogenic EBV peptides estimated suitable for a protective vaccine were selected according to rational strategy, which combined the sequence based antigenicity prediction of B cell and T cell epitopes (by considering the protective/neutralizing immune responses and pathogenicity mechanisms) with the supertype affinity along with the specificity of prevalent HLA alleles as well as HLA ligand conservation (Sollner J. et al. Immunome Res. 2008; Immunome Res. 2010). Altogether 15 epitopes were selected out of the 52 immunogenic peptides considered. The epitopes (oligopeptides) were coupled to biocompatible microparticles (larger than 100 μm) in precise relative amounts; always 3 peptide combinations created together 19 putative immunogenic mixes in different variations. To each of microcarrier beads one pattern receptor recognizing (PRR) agonist (such as poly I/poly C, CpG and/or R848/resimiquod) was ligated. The 19 putative peptide vaccine mixes in question were used to immunize 3 rabbits in 19 immunization groups, which were challenged with the high EBV dose as above described. Taken together, 2 control groups had been created: those from the preliminary experiment (control A, 21 rabbits) and the group of 3 animals (control B) included into the protection test. The results reflecting the four most reliable infection markers (EA-D ELISA, immunoblot, EBV DNA and LMP1 antigen detections) as determined in control A experiment, were included into efficacy calculations. In these, the positive rates obtained in each immunized group were compared with the frequency of data rates in either of the 2 control groups. At least 5 oligopeptide combinations (immunization groups no. 1, 6, 12, 15 and 18), which contained 7 of the 15 predicted epitopes, comprised the statistical category revealing a considerable or (at least) good protective effect (the total frequency of positive data rates ranged here from 0 to 5% while no EBV DNA was detected). Furthermore, a category of slight protection has emerged (revealing positive data rates up to 20%), which contained 7 immunization mixes (numbers 9, 10, 13, 14, 16, 17 and 19). No effect (positive data rates over 21%) was seen after immunization with the rest of 7 mixes (immunization groups numbers 2, 3, 4, 5, 7, 8 and 11), in which the data positive rates showed no statistically significant difference as compared to both controls. Three of the protective epitope carrying polypeptides were structural (envelope) glycoproteins another 3 were non-structural and/or latency associated proteins. In addition to the 6 protective EBV-coded proteins which had already been declared for immunogenic by others (reviewed by Rajcani et.al., in Recent Patents on Anti-Infective Drug Discovery, submitted), we found one non-structural polypeptide not reported yet in such context. Julius.Rajcani@savba.sk

Ian Tizard

Texas A&M University College of Veterinary Medicine, USA

Title: A Unique Virus-Mediated Neurologic Disease Causing Intestinal Paralysis In Birds

Time : 14:25-14:45

Biography:

Tizard obtained his degree in Veterinary Medicine from the University of Edinburgh and his PhD from the University of Cambridge. He is currently University Distinguished Professor of Immunology and Richard M. Schubot Professor of Exotic Bird Health at Texas A&M University. His current research focuses on vaccines administered by the intranasal and oral routes, as well as studies on viruses of wild and exotic birds. He is also involved in whole genome sequencing of several avian species.

Abstract:

The bornaviruses are negative stranded RNA viruses with the unique ability to replicate within the nucleus of infected cells. There are multiple genotypes of these viruses, the great majority affect birds and are classified asAvian bornaviruses (ABV). One genotype causes Borna disease in mammals and hence is named Borna disease virus (BDV). All the bornaviruses invade the central nervous system. Under some circumstances they cause an acute lethal encephalitis. However in many birds, while they infect the brain but do not cause significant disease. These birds survive indefinitely as apparently healthy carriers. Avian Bornavirus infects numerous species of parrot, waterfowl such as ducks, geese and swans, gulls, raptors and some finches. The spectrum of resulting disease extends from asymptomatic carriage through encephalitis of variable severity, blindness, ataxia and inability to fly to acute proventricular dilatation and intestinal blockage. It is this last syndrome, called proventricular dilatation disease (PDD) that is of major significance in captive birds. The pathogenesis of PDD is unknown. Affected birds develop a polyneuritis with detectable virus, not only in the brain and spinal cord, but also in the vagus and sciatic nerves and in the autonomic ganglia of the anterior gastrointestinal tract. However ABV is not cytopathic so the neuronal inflammation is not secondary to virus-mediated cytotoxicity. Likewise vagotomy does not result in proventricular dilatation suggesting tat the key lesion is not in the vagus.In laboratory rodents infected with Borna disease virus, nervous system lesions are most likely mediated by cytotoxic T cells since anti T cell serum or appropriate immunosuppression can ameliorate the disease. It is unclear whether this also applies to ABV/PDD although in our hands preliminary treatment with cyclosporine is giving encouraging results. It has been asserted that PDD may also develop as a consequence of the development of a Gullain-Barre-like syndrome associated with the development of antiganglioside antibodies. Certainly such antibodies may be detected in some cases (as may anti-myelin antibodies), but the correlation between antibody levels and disease severity is poor.There is however a correlation between the level of anti ABV antibodies in serum and the severity of disease. In our studies seroconversion is associated with the onset of severe clinical disease. Additionally the close association between the viral ribonuclear complex and the histones in chromatin implies that the virus may mediate significant epigenetic effects within infected neurons.

Biography:

Abstract:

Several studies have demonstrated that sulfated polysaccharides (PS) extracted from sea algae have antiviral properties and are much less cytotoxic than conventional antiviral drugs. Fucoidan and Ulvan are PS found in brown and green algae respectively.Newcastle Disease Virus (NDV) is a paramyxovirus causing fatal infections of poultry. This study aims to determine the antiviral activity and mechanism of action in vitro, for the Cladosiphon okamuranus fucoidan, the Ulva clathrata ulvan, and the mixture thereof against NDV La Sota strain. The antiviral activity was tested using syncytia formation, the assays were performed adding the compounds during all infection cycles to determine the 50% effective concentration (EC50), further, we determined in vitro the 50% cytotoxic concentration (CC50) for define therapeutic index (TI) (CC50/EC50).Sulfated polysaccharides showed potent antiviral activity with a TI > 800,000. In contrast, ribavirin had low activity and considerable cytotoxicity(TI 1.7). Neither PS showed virucidal effect. In time-of-addition studies, fucoidan inhibited viral infection at early stages (0 to 60 minutes post-infection), reducing attachment protein expression (HN) by 98%. In a fusion inhibition assay, PS significantly inhibited syncytia formation when they were administered before the cleavage of fusion protein. The mixture of PS shows a little bit more antiviral activity than each one alone.In an in ovo system, fucoidan significantly suppressed viral NDV RNA synthesis by 99.8%. These data show that PS could be a potent antiviral compounds for clinical and/or veterinary use and also provide a better understanding of the mode of antiviral action of PS.

Susan L. Payne

University College of Veterinary Medicine and Biosciences
USA.

Title: Avian Bornavirus: A Common and Emerging Pathogen in North America

Time : 11:45-12:05

Biography:

S. Payne completed her Ph.D. at Louisiana State University. She did post-doctoral work in virology at LSU and has held faculty positions at Case Western Reserve University Medical School and the University of Texas at Arlington. She is currently a tenured associate professor at Texas A&M University. Dr.Payne has published over 45 peer reviewed publications and book chapters in the subject areas of retroviruses and bornaviruses. She carried out NIH funded studies on the replication and virulence determinants of equine infectious anemia virus (EIAV).She is currently studying bornaviruses in wild waterfowl and investigating the role of autoimmunity and pathogenesis in the outcome of avian bornavirus infections of cockatiels and ducks. She has mentored numerous students and currently teaches at the professional, graduate and undergraduate levels while continuing studies of Avian Bornaviruses.

Abstract:

In the 1970s a fatal disease emerged in captive parrots.Clinical signs included encephalitisand gut paralysis leading to proventricular impaction. Thus the disease was called proventricular dilatation disease (PDD). In 1991 PDDwas described in a small number of wild Canada geese. In 2008, avian bornaviruses (ABV) were isolated from symptomatic parrots. Bornaviruses are negative sense, unsegmented RNA viruses (Order Mononegavirales, Family Bornaviridae);the type-virus is Borna disease virus (BDV). Bornaviruses replicate in the nucleus, are noncytopathicand cause persistent infections. BDV causes sporadic outbreaksof neurologic disease among horses in Central Europe. At least seven distinct avian bornavirus genotypes infect captive parrots. Canaries and finches have distinct ABVs and we isolateda genotype from wild waterfowl in North America. Called ABV-Canada goose (ABV-CG) this virus is found in geese and swans.Some ABV-CG infected birds suffer from severedigestive and/or neurologic abnormalities.Histopathology reveals lymphocytic infiltrates and ABV antigens can be detected using immunohistochemistry.We recently isolated a newABV genotype from mallards. We found high levels of virus in the brain and retina of a hunter killed bird. It is not clear what impact ABV infection has on waterfowl populations although it is clearly associated with neurologic disease in some birds. In addition waterfowlstudies, we areactively studying ABV replication and pathogenesis incockatiel and duck models. This work focuses on elucidating the role of virus andautoimmunity in thepathogenesis of PDD, as based on prior studies on BDV, the disease is believed to have a significant autoimmune component

Biography:

• Joined JUST Sept. 2004 as Assistant Professor and promoted to Associate Professor in Sept. 2009. • Chairman of the Departments of Applied Biological Sciences and Biotechnology and Genetic Enigneering since Sep. 2007 till present. • Promotion reports were sent to Harvard Medical School, University of Pennsylvania and University of Iowa. All of the reports were very strong positive however; the Referee at Harvard Medical School said “based on his academic record, Dr. Jaradat would even be promoted at Harvard University”. • Supervised 8 MSc students as main advisor and 10 MSc students as co-advisor • Examiner on 5 MSc thesis in JUST and Jordan University. • Published 27 articles, reviews and Book chapters in Refereed Journals. • Present research work in 17 conference posters and 3 oral presentations. • Isolated and identified 29 strains of Cronobacter sakazakii from Jordan, and sequenced their 16S rRNA and deposited the 29 sequences in the GenBank (BMC Microbiology, 2009. 9:225). • Deposited 9 new Cronobacter isolates from Jordan in the Egyptian Microbial Culture Collection (EMCC). • Obtained 11 grants as principal investigator and 11 grants as co-investigator. • Member Elect in the University Council, 2009/2010. • Prepared and taped science modules in conjunction with MIT center for distance learning (Biotechnology Module). • Participated in the development of an MSc program in Integrated Water Resources Management and subsequently developed a course in Environmental Pollution in conjunction with University of Michigan, Ann Arbor and Cornell University and sponsored by USAID. • Several of my published articles on pathgenicity of Listeria monocytogenes appeared in several news reports

Abstract:

Infectious bronchitis virus (IBV) and Avian Influenza subtype H9N2 are very dynamic and evolving viruses, causing major economic losses to the global poultry industry. Respiratory disease outbreaks affecting different poultry farms were investigated. Two IBV isolates (JOA2, JOA4) along with two H9N2 isolates were detected by RT-PCR. Strain identification was done by sequencing and phylogenetic analysis of the amplified hypervariable region of the spike 1 (S1) gene of IBV and complete HA sequencing for H9N2 isolates. These two IBV isolates were found to be of the IBV strain CK/CH/LDL/97I of the J2 group, while the HA gene of the two H9N2 isolates were found to be of the new group B. The presence of these new IBV and H9N2 isolates may account for vaccination failure against IBV and H9N2, since all these viral isolates were from vaccinated chicken flocks.

  • Track 14: Recent Advances in Drug Discovery

Session Introduction

Baoming Jiang

Centers for Disease Control and Prevention, USA

Title: Skin immunization against rotavirus using microneedles

Time : 11:25-11:45

Biography:

Jiang currently is a team lead/supervisory research microbiologist in Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, US Centers for Disease Control and Prevention. His research interests include epidemiology, virology, immunology and vaccinology of rotavirus and other agents of viral gastroenteritis, with a particular focus on research and development, and advocacy of rotavirus vaccines. He has served as an advisor and consultant for vaccine manufacturers, government and non government organizations in developed countries and emerging developing countries. Dr. Jiang obtained his DVM degree in China and PhD degree in virology from the Ohio State University, and received post-doctoral training with the National Research Council of the National Academy of Sciences at CDC. He has published more than 130 articles or book chapters in peer-reviewed scientific journals and holds several patents on rotavirus vaccine and diagnostics. He received a number of awards and honors, including the 2012 Excellence in Technology Transfer Award from the Federal Laboratory Consortium for “Heat Inactivated Rotavirus Vaccines” and the 2014 Honor Award from the Centers for Disease Control and Prevention for Excellence in Public Health Impact in supporting domestic rotavirus surveillance in the United States. He has served in various professional and community organizations, including ATCC Advisory Committee, editorial and review boards of scientific journals, and overseas Chinese communities. His other personal interests include travel, sports and gardening.

Abstract:

Despite progress in the prevention of rotavirus following the introduction of rotavirus vaccines in middle income and developed countries, diarrheal disease remains a major killer among children in low-income countries of Africa and Asia. The lower efficacy of live oral vaccines, the need for a separate supply chain with large volume of cold storage, and the perceived concern about adverse events (e.g., intussusception) all point to the need for a second generation of parenteral vaccine. In our early studies, we demonstrated high immunogenicity and protective efficacy of an inactivated rotavirus vaccine (IRV) when formulated with aluminum adjuvant and administered intramuscularly (IM) in mice and gnotobiotic piglets. We recently assessed new technology to deliver rotavirus vaccine and demonstrated dose sparing and enhanced immunogenicity of IRV without adjuvant administered intradermally (ID) using a microneedle patch in mice. In the present study, we further assessed whether IRV without adjuvant when administered ID using a microneedle device MicronJet600® could induce protective immunity and confer protection in comparison with aluminum-adjuvanted IM-administered IRV in neonatal gnotobiotic piglets. Three doses of 5 μg IRV when administered by ID and 5 μg IRV formulated with 600 μg Al(OH)3 when administered by IM induced comparable IgG, IgA, and neutralizing titers in serum of piglets. Both IRV immunization regimens protected piglets from oral challenge with a virulent human RV Wa strain, as evidenced by reduction in or lack of rotavirus antigen shedding in stool and lower mean diarrhea scores. By contrast, placebo-vaccinated piglets shed rotavirus antigen for up to 7 days or developed diarrhea. These findings demonstrate the immunogenicity and protective efficacy of IRV in a large animal model and further help establish the proof of concept for IM and ID immunization against rotavirus.

Biography:

William Mitchell completed his MD from Vanderbilt University, was a house officer on Osler Medicine at Johns Hopkins Medical Center, and received his PhD in Biochemistry from Johns Hopkins University. He is Board certified in Clinical Pathology and serves as Professor of Pathology, Microbiology, and Immunology at Vanderbilt School of Medicine. He is an independent member of the Board of Directors for Hemispherx Biopharma (Philadelphia, PA) and Chronix Biomedical (San Jose, CA/ Göttingen, Germany).

Abstract:

The Toll-Like Receptors (TLRs) represent a family of class I transmembrane receptors that are elements of an ancient system of immune response to pathogen associated molecular patterns (PAMPs). TLR3 uses a unique non-MyD88 intracellular signaling pathway to induce innate immune responses including Type 1 interferons (IFN) with reduced inflammatory responses compared to the MyD88 pathway used by the other nine TLRs. The PAMP for TLR3 is dsRNA. Mis-matched base pairing configuration of the two RNA strands (rintatolimod) restricted binding to TLR3. Homologous dsRNA strand base pairing activates TLR3 and cytosolic helicases using the pro-inflammatory MyD88 pathway. Emerging human viral pathogens represent major potential hazards to human populations in which innate immune defenses of the host are compromised. Recent emerging viruses with high lethality in humans include the avian influenza viruses and the human coronoviruses. As example there are six known human coronoviruses (Hu-CoV), four of which are responsible for mild “cold-like” symptoms. Two (MERS-CoV and SARS-CoV), however, have evolved an infectious advantage over the four mildly pathogenic human coronoviral species by inhibition of innate immune responses. Multiple components of MERS-CoV (M, ORF 4a/b, and ORF 5) inhibit the de novo production of a key component of innate immunity, interferon (IFN),that is an induction product of TLR3 activation. Data demonstrate that natural IFN (Alferon) as well as restricted activation of TLR3 by rintatolimod protect cells and/or animals from infection by emerging viral pathogens or cytokine storm associated pathology.