Day 1 :
Keynote Forum
Tomasz Pniewski
Polish Academy of Sciences, Poland
Keynote: Low-dosed lyophilised plant tissue bearing VLPs of HBV small surface antigen as an oral booster vaccine against hepatitis B
Time : 09:00 AM
Biography:
Tomasz Pniewski has completed his PhD at the age of 29 years from the Institute of Bioorganic Chemistry PAS and postdoctoral studies from Thomas Jefferson University, Philadelphia, USA. He has worked in the Institute of Plant Genetics PAS since 2003. He is the head of Biotechnology Department there, and for two years worked also in the Wielkopolska Centre of Advanced Technologies as an expert for organisation and equipment. He has published more than 25 papers in reputed journals and has gained 6 patents on plant-derived vaccines.
Abstract:
The continued HBV high prevalence coupled with deficiencies in vaccination programmes stimulate research on a new type of vaccines. Potential orally administered plant-based vaccine is highly attractive regarding efficacy, cost-effectiveness and availability of mass hepatitis B prevention. Freeze-dried oral formulations facilitate elimination of complex purification steps, size reduction and better stability during storage, as well as ensure controlled administration regime in minimised medical facilities.
The aim of presented study was to develop a lyophilisation protocol facilitating successful processing of lettuce leaf tissue containing S-HBsAg formed into VLPs (Virus-Like Particles). Several drying profiles and excipients as well as effects of freezing rate and post-process residual moisture were analysed. The profile of 20ºC for 20 h for primary and 22ºC for 2 h for secondary drying as well as sucrose proved the most efficient stabilisation of S-HBsAg during freeze-drying. The process was highly reproducible (86 - 97%), and provided a product with VLP content up to 200 µg/g DW. Atmosphere of nitrogen proved to preserve S-HBsAg VLPs for minimum one year at temperatures up to 37°C. Animal trials confirmed immunogenicity of processed tissue powder with S-HBsAg, used as an oral booster vaccine. Low-dosed (5 -200 ng) preparation elicited anti-HBs response at level of commercial injection vaccine (around 1000 mIU/ml), together with growth population of specific B and T lymphocytes and only slightly increased population of Tregs.
As a result, a plant-derived semi-product with good long-term stability and immunogenicity of S-HBsAg was obtained for the definite formulation of oral booster vaccine against HBV.
Keynote Forum
Hina J. Panchal
Icahn School of Medicine at Mount Sinai, USA
Keynote: Survival outcomes in liver transplant recipients with Model for End-stage Liver Disease scores of 40 or higher: a decade-long experience
Time : 09:45 AM
Biography:
Hina J. Panchal, Department of Genetics & Genomic Science and Gastroenterology, Icahn School of Medicine at Mount Sinai, Liver transplantation in recipients with MELD scores of ≥40 offers acceptable longterm survival outcomes. Futility predictors indicate the need for prospective follow-up studies to define the population to gain the highest benefit from this precious resource.
Abstract:
Background: The Model for End-stage Liver Disease (MELD) has been used as a prognostic tool since 2002 to predict pre-transplant mortality. Increasing proportions of transplant candidates with higher MELD scores, combined with improvements in transplant outcomes, mandate the need to study surgical outcomes in patients with MELD scores of ≥40. Methods: A retrospective longitudinal analysis of United Network for Organ Sharing (UNOS) data on all liver transplantations performed between February 2002 and June 2011 (n = 33 398) stratified by MELD score (<30, 30–39, ≥40) was conducted. The primary outcomes of interest were short- and longterm graft and patient survival. A Kaplan–Meier product limit method and Cox regression were used. A subanalysis using a futile population was performed to determine futility predictors. Results: Of the 33 398 transplant recipients analysed, 74% scored <30, 18% scored 30–39, and 8% scored ≥40 at transplantation. Recipients with MELD scores of ≥40 were more likely to be younger (P < 0.001), non-White and to have shorter waitlist times (P < 0.001). Overall patient survival correlated inversely with increasing MELD score; this trend was consistent for both short-term (30 days and 90 days) and longterm (1, 3 and 5 years) graft and patient survival. In multivariate analysis, increasing age, African-American ethnicity, donor obesity and diabetes were negative predictors of survival. Futility predictors included patient age of >60 years, obesity, peri-transplantation intensive care unit hospitalization with ventilation, and multiple comorbidities. Conclusions: Liver transplantation in recipients with MELD scores of ≥40 offers acceptable longterm survival outcomes. Futility predictors indicate the need for prospective follow-up studies to define the population to gain the highest benefit from this precious resource.
Keynote Forum
ESCHLIMANN Marine
Lorraine University, France
Keynote: Hepatitis B Virus envelope variability of genotype A strains correlated with HBsAg persistence in patients with acute or chronic hepatitis B and in HBV/HIV co-infected patients.
Biography:
Marine ESCHLIMANN is a PhD student, currently the second year of her thesis. After a license in Cell Biology and Animal Physiology at the Faculty of Sciences, Reims, France, she focused on Microbiology in the Master BioMANE at the Faculty of Sciences, Nancy, France. After a study on bacterial biofilms, she was involved in a research program in Virology, in the University of Medicine, Nancy, France, with Pr E. Schvoerer et al. Thus she contributed to several investigations on the variability of HBV envelope proteins with the support of a ministerial scholarship.
Abstract:
Around 240 million people are chronically infected by Hepatitis B virus (HBV) worlwide. The clearance of HBV surface Antigen (HBsAg) correlated with a good clinical prognosis is rarely achieved, even on anti-HBV treatments. HBV envelope proteins play a crucial role in virus cellular entry and in immune recognition. Our hypothesis is that the variability of HBV envelope proteins could influence HBsAg clearance or persistence, as suggested in our previous study on HBV genotype D (Velay et al., JVH, 2016). This study was extended to HBV genotype A infected patients with different clinical profiles: acute (n=4) or chronic hepatitis B (n=6) and HBV/HIV coinfection under treatment (n=6). In each group, patients with HBsAg clearance (Resolvers-R) were compared to Non-Resolvers (NR). For this purpose, HBV S and preS sequences were studied by bulk genotyping and ultra-deep sequencing (UDS). Amino acid sequences were analized with bioinformatics for predicted antigenicity. More frequent major mutations were observed in S gene than in preS region (p=0.02 in acute HBV infection). Among mutations found exclusively in NR, nine were observed several times (W4stop, T173K/A in preS; R79H, T118A, F134Y, Y161F, E164D, V209L in S). The mutation sY161F, found in four NR, leaded to a decrease in predicted antigenicity (22.6%). In the pol gene overlapping the S gene, the number of mutations tended to be higher in treated than in untreated patients (7.7 vs 3 mutations/patient). These results argue in favor of an influence of HBV envelope variability on the evolution of Hepatitis B in various clinical contexts.
Keynote Forum
Kusnandi Rusmil
Sadikin General Hospital, Indonesia
Keynote: Clinical Trials of Hepatitis B Vaccine
Biography:
Hepatitis B is one of the most common infectious diseases. Two billion people worldwide have serologic infections, while 350 million are chronically infected and at risk for HBV-related liver disease. Indonesia has moderate–high (9.4%) endemicity for hepatitis B infection. 90% of infants infected with HBV are due to perinatal transmission, 30-50% of HBV-infected children under 5 years old are known to be Hepatitis B carrier, and 6-10% of HBV-infected adult are suffering from chronic liver diseases. Hepatitis B immunization is recommended for infants after birth.
Several studies have reviewed the immunogenicity and safety of hepatitis B vaccine (Bio FarmaÒ), such as in early age group in 2003–2004, in adolescent in 2012, used in combination with pentavalent vaccine in 2013, and booster continuation at the age of 18–24 months in 2014. Clinical trial studies of 3-doses of monovalent hepatitis B vaccine in children receiving basic immunization, and additional 3-doses monovalent hepatitis B vaccine in hypo-/non-responder children receiving basic immunization have shown that all children achieved level of anti-Hbs titer >10 mIU/mL. Three doses of monovalent hepatitis B vaccine given to adolescent who had never been immunized before proven to be safe and provide immunity.
Basic and booster immunization of hepatitis B combination/pentavalent (DPT-HB-Hib) at 18–24 months has been proven to be safe and provide the immunogenicity. Hepatitis B vaccine manufactured by Bio Farma Inc., given during basic and booster immunization, including the monovalent and combination vaccine, have been shown to be safe and provide good immunogenicity.
Abstract:
Kusnandi Rusmil has completed his Doctor Program from Universitas Padjadjaran Bandung. He is a Professor and the Head of Social Pediatric-Growth and Development at Department of Child Health Hasan Sadikin Hospital/Faculty of Medicine Universitas Padjadjaran, a chairman of Growth and Development-Social Pediatric Working Group Indonesian Pediatric Society 2002 untill 2011, a member of Immunization Task Group on Indonesian Pediatric Society, and also a member of Indonesian Technical Advisory Group on Immunization (ITAGI) for Ministry of Health Republic Indonesia. He has been a chief of Adverse Event Following Immunization West Java Committee, and an advisor of AEFI Bio FarmaÒ. He published some papers and presented it in international, local scientific journal and conference.