Day 2 :
University of California, USA
Time : 09:30
James D. Cherry MD, MSC has been a pediatric infectious diseases specialist for 53 years. He is a Distinguished Research Professor at the David Geffen School of Medicine at University of California, Los Angeles. Professor Cherry has published 304 research papers, 108 editorials/commentaries and 282 book chapters. He has given 238 presentations at national and international conferences. The majority of these papers and talks have related to vaccines and vaccine preventable diseases. Professor Cherry is the senior editor of Feigin and Cherry’s ”Textbook of Pediatric Infectious Diseases” which is now in its 7th edition.he was Chief of the Division of Pediatric Infectious Diseases for 27 years. He has received numerous awards, including the Distinguished Physician Award from the Pediatric Infectious Diseases Society in 2003 and the UCLA Medical Alumni Associations’ Medical Science award in 2005.
About 10 years ago, C. Paddock and I and other colleagues studied the pathological findings in 15 young infants whose deaths were caused by B. pertussis infection. The resulting hypothesis at the time was that refractory pulmonary hypertension had occurred as a result of aggregates of mixed leukocytes in small blood vessels in the lungs. With my associates at the California Department of Public Health and a number of pediatric infectious diseases specialists in California, we have done 4 studies relating to risk factors for death and pulmonary hypertension in young infants with pertussis. In the first study risk factors were (1) high and rapidly rising WBC counts; (2) high and rapidly rising pulse and respiratory rates and; (3) pneumonia with early onset. The second study was a case-control study involving 53 deaths and 183 controls. This study confirmed the findings in the previous study and in addition noted numerous other possible risk factors. Fatal cases had significantly lower birthweight, younger gestational age, and younger age at time of cough onset. Fatal cases were less likely to have received macrolide antibiotics and more likely to have received steroids and/or nitric oxide therapy. In a third study, we evaluated 10 young infants who received exchange blood transfusion therapy; there were 5 survivors and 5 deaths. None of the survivors had shock/hypotension or organ failure whereas the death cases all had shock/hypertension and 3 had organ failure. The final study is a study of exchange transfusion or non-exchange transfusion in severe infant pertussis cases. Analysis of data from this study suggests that conventional treatments for pulmonary hypertension in pertussis may be harmful.
University of Southern California, USA
Time : 10:15
Charles McKenna is Professor of Chemistry, Pharmacology & Pharmaceutical Sciences at the University of Southern California (USC), where he is also Director of the USC Center for Drug Discovery. He received his Ph.D. in Chemistry at UC San Diego and was an NIH postdoctoral Fellow at Harvard University. His research interests are primarily in medicinal and organophosphorus chemistry, focusing on design of novel chemotherapeutic agents, bisphosphonate imaging probes for bone, and nucleotide probes of DNA polymerases. Author of over 225 publications and patents and the recipient of numerous awards for his research and teaching, Dr. McKenna has founded several biotech companies.
Human adenoviruses (AdV) cause generally mild infections of the respiratory and GI tracts as well as some other tissues. However, certain serotypes are associated with acute respiratory disease and epidemic keratoconjunctivitis. AdV can cause serious infection in severely immunosuppressed individuals, and pediatric patients undergoing allogeneic hematopoietic stem cell transplantation have mortality rates up to 80% with disseminated disease. Despite this significant challenge to health, there are no drugs approved specifically to treat AdV infections. Cidofovir, an analog of cytidine monophosphate which acts as an AdV DNA chain terminator, is used clinically, but has several drawbacks, including relatively low cellular potency and lack of oral bioavailability. USC-087, a novel N-alkyl tyrosinamide phosphonate ester prodrug of HPMPA, the adenine analogue of cidofovir, is markedly more potent than the parent drug or cidofovir itself against multiple AdV types in cell culture. USC-087 is also effective orally against AdV-C6 in a cyclophosphamide immunosuppressed permissive Syrian hamster model. Injection of AdV-C6 (or AdV-C5) intravenously leads to a disseminated infection that resembles the human disease. USC-087 completely prevented or significantly decreased mortality when administered orally up to 4 days post challenge with the median lethal intravenous dose of AdV-C6. USC-087 also prevented or significantly decreased liver damage caused by AdV-C6 infection, and suppressed virus replication up to 4 days post challenge. The potential and scope of the N‑alkyl tyrosinamide ester prodrug approach will be discussed.
University of Texas, USA
Keynote: Ebolavirus GP stalk-specific antibodies from survivors effectively target multiple steps of viral infection
Time : 11:20
Prof. Bukreyev has completed his PhD in 1993 and completed his postdoctoral studies at the National Institute of Allergy and Infectious Diseases, NIH. He is professor at the University of Texas Medical Branch at Galveston. His laboratory focuses on development of vaccines against highly pathogenic viruses filoviruses Ebola and Marburg and on investigation of mechanisms of their high pathogenicity. He has published more about 90 papers in reputed journals including Science, Cell, Journal of Clinical Investigation, PNAS, PLOS Pathogens, The Lancet, Journal of Virology, Vaccine and others. He is a member of NIH Vaccines Against Microbial Diseases Study Section.
Recent studies suggest that some glycoprotein (GP) specific monoclonal antibodies (mAbs) can protect experimental animals against the filovirus Ebola virus (EBOV). Multiple mAbs have been isolated previously from blood samples of human survivors of natural Bundibugyo ebolavirus (BDBV) infection (Flyak A. et al., Cell 2016). A panel of mAbs from four individual donors has been selected to study the mechanisms of infection inhibition. BDBV41 and BDBV289 mAbs specific to GP glycan cap (GC) inhibited virus attachment to the cells, whereas stalk-specific BDBV259, BDBV317 and BDBV223 mAbs were able to traffic to endosomal compartments together with virions and block the late steps of entry. BDBV270 and BDBV289 GC mAbs and BDBV317 mAb targeting membrane proximal external region (MPER) dose-dependently inhibited cell-to-cell viral transmission, which corresponded to the observed differences in mAb efficiency against high multiplicity of infection. The egress of virus from infected cells was suppressed by all glycan cap-specific mAbs, with strongest inhibition observed for the single non-neutralizing BDBV52 mAb. BDBV223 MPER mAb showed superior antiviral activity in vitro at each step of viral replication analyzed. In time course experiments, only MPER mAbs inhibited virus replication when added post-infection. The activation and degranulation of natural killer cells and monocyte phagocytosis relied mostly on IgG subclass, with the highest levels demonstrated by IgG3 mAbs. Finally, MPER mAbs conferred full protection against EBOV infection in mice. Altogether, these results suggest usage of mAbs with different epitope specificity could complement inhibition of multiple steps of filovirus infection through Fab- and Fc-mediated mechanisms.