Day 2 :
Keynote Forum
Ronald Moss
Ansun Biopharma,USA
Keynote: DAS181: A Novel Host Directed Approach to Prevent and Treat Virus Infections
Time : 08:00-08:25
Biography:
Ronald Moss, M.D. has served as the Chief Executive Officer of Ansun Biopharma, Inc. since October 2012, and before that, served as both interim CEO and Executive Vice President of Clinical Development and Medical Affairs at Ansun from 2008 to 2012. Dr. Moss has held various executive positions in the pharmaceutical industry for over 20 years and has played a pivotal role in successfully leading companies through the complexities of drug and vaccine development. Dr. Moss has been involved in drug and vaccine development of products in Infectious Disease, Allergy, Neurology, Dermatology, Oncology, Respiratory, Transplant, and Autoimmunity in both large pharmaceutical and biotechnology companies, including roles at Aventis, Immune Response, Merck, Telos and Vical. He has also authored over 70 scientific publications. Prior to joining industry, he received his M.D. degree from Chicago Medical School, completed a residency in pediatrics at SUNY Stony Brook and completed a fellowship at the National Institutes of Health. He is double boarded in Pediatrics and Allergy and Immunology. He is also a Fellow of the American Academy and American College of Allergy and Immunology.
Abstract:
Vaccines and antivirals are currently the main approaches to prevent and treat respiratory virus infections such as influenza. The recent 2009 H1N1 pandemic and the H7N9 outbreaks exemplify the unpredictable nature of influenza viruses. Particularly concerning is the documentation NAI drug resistance to particular strains of influenza. DAS181, is an investigational host directed inhaled sialidase fusion protein and has shown in vitro and in vivo activity against many subtypes and strains of influenza virus including H7N9 and H5N1. Data will be presented from preclinical and late stage clinical studies of DAS181 against influenza. Parainfluenza lower track infection results in significant morbidity and mortality in immune-suppressed transplant patients without any licensed vaccines or antiviral drugs. In addition, the drug has shown in vitro and in vivo activity against parainfluenza virus strains (PIV-1, PIV-2, PIV-3, and PIV-4) by inactivating the virus binding receptors. DAS181 has been utilized in over 80 EIND’s, and a phase 1 study of transplant patients with severe PIV infection. Interestingly, DAS181 has also shown significant in vitro activity against other viruses including EV-68, JC, and BK. The host directed approach of DAS181 contrasts with virus specific antivirals, by circumventing considerable problems related to antiviral drug resistance, and the need for prediction of strains for effective vaccines. DAS181, an investigational drug, is currently in Phase 2 clinical trials of parainfluenza infection. Preclinical and clinical data from studies with DAS181 activity against a variety of pathogenic viruses will be presented.
Keynote Forum
Angel S. Galabov
Bulgarian Academy of Sciences,Bulgaria
Keynote: Triple Combination of Antivirals Following a Treatment Course by Consecutive Alternating Administration Interferes the Development of Drug Resistance in Enterovirus Infections in Mice
Time : 08:25-08:50
Biography:
Dr. Angel Simeonov Galabov is a professor of virology in The Stephan Angeloff Institute of Microbiology, Sofia, Bulgaria. He completed his Ph.D. at Bulgarian Academy of Sciences and M.D at Higher Medical School, Sofia, Bulgaria. He held many positions in his carrier. He is Regular Member of the Bulgarian Academy of Sciences and is a member of several other Scientific Organizations. He has 40 patent inventions and 235 scientific refereed publications, including a monograph and chapters in books. He received award and honors; Awarded by the Bulgarian Academy of Sciences by the Sign of Honor “Marin Drinov†in 2009.
Abstract:
Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, and the chronic obstructive pulmonary disease. The above diseases along with significantly high morbidity and mortality in children, in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the lots of work carried out in this field. The main reason for this is the development of drug resistance. . We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, CVB infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50o C, pathogenicity in mice) for characterization the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. rnThe monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action resulting in the selection of a number of very effective in vitro double combinations revealing synergistic character of the combination effect and a broad spectrum of sensitive enteroviruses. The most prospective attainment in our study in this field was the development of a novel scheme for the combined application of anti-enteroviral substances in coxsackievirus B1 and B3 neuroinfections in newborn mice. It consisted of a consecutive, alternating and non-simultaneous, administration of the substances in the combination. The triple combinations disoxaril/guanidine/oxoglaucine (DGO), pleconaril/guanidine/oxoglaucine (PGO) and pleconaril/MDL-860/oxoglaucine (PMO) showed a high effectiveness expressed in a marked reduction of mortality rate in infected mice as compared both to the placebo group, and to the partner compounds used alone every day, and to the same combination applied simultaneously every day. Studies of the drug sensitivity of viral brain isolates from mice, treated with these combination showed not only preserved, but even increased sensitivity to the drugs included in the combination. Obviously, the consecutive alternating administration of anti-enteroviral substances hinders the occurrence of drug-resistance in the course of the experimental enteroviral infections in mice. rn
Keynote Forum
Sita Awasthi
University of Pennsylvania,USA
Keynote: Immunogenicity evaluation of a subunit vaccine for genital herpes in Rhesus macaques
Time : 08:25-08:50
Biography:
Sita Awasthi has received her Ph.D in Biochemistry from Devi Ahilya University at Indore, India and her postdoctoral training from University of Pennsylvania at Philadelphia. Currently she is a Research Assistant Professor at University of Pennsylvania, Pearlman School of Medicine, Infectious Disease Division. Her research interests are HSV-2 vaccine development against genital herpes disease and HSV-2 HIV-2 co-infections. She has published numerous research articles and serving as an editorial board member of Journals of antivirals and anti retrovirals, Journal of Immunoassay and Immunochemistry.
Abstract:
About 500 million people are infected with Herpes Simplex Virus type 2 (HSV-2) worldwide. Genital HSV-2 infection is one of the major causes of genital ulcer disease and the risk of HIV-1 acquisition and transmission by 3-4 fold in humans. Efforts to prevent genital ulcer disease with acyclovir failed to reduce HIV-1 acquisition or transmission, supporting the need for an effective vaccine. We developed a trivalent gC2/gD2/gE2 (HSV-2 glycoprotein C, D and E) subunit vaccine that generates high levels of neutralizing antibodies, blocks HSV-2 immune evasion from complement, blocks IgG-Fc binding to the HSV-2 IgG Fc receptor, and is highly efficacious in preventing genital disease and viral shedding in guinea pigs. Here we present an immunogenicity evaluation of gC2/gD2/gE2 vaccine in macaques. Female macaques were immunized three times four weeks apart with 20ïg of each gC2, gD2, and gE2 glycoprotein or 20ïg gC2 alone with CpG and alum as adjuvants. After the third immunization, plasma analysis showed high titer antibody responses to each antigen, high titer neutralizing antibodies, and antibodies that blocked complement C3b binding to gC2 and IgG Fc binding to gE2. Six months after the third vaccination, the immune responses to each glycoprotein had declined 2-3 fold, but boosted within 2-weeks after a booster immunization administered at 9 months. Additionally we detected antigen specific antibody response in vaginal fluid. Importantly, analysis of PBMCs from macaques that were immunized with gC2 alone, showed a gC2 specific CD8 T cell response after 3 immunizations. In addition, antigen specific poly-functional CD4 T cell responses are induced in the trivalent vaccine group. Our results show that the trivalent gC2/gD2/gE2 subunit antigen vaccine generates highly potent immune responses in Rhesus macaques and may prove to be a promising genital herpes vaccine candidate for future trials in human.