Day 3 :
Pharmaceuticals TetraQ, Australia
Keynote: Modern vaccine delivery systems
Time : 9:00-9:30
Professor Toth is a chemical engineer with a research focus on medicinal chemistry. He was awarded his PhD in 1972 and has since worked in Hungary, Canada and the United Kingdom before relocating to Australia in 1998. His major research interests are drug delivery, immunoadjuvants, synthetic vaccines and gene delivery. His research has attracted over $60 million in competitive grants, research contracts and investment funds in the past 10 years. He has over 300 peer-reviewed publications, 43 patents, and an excellent track record in research commercialization as a key founder of Alchemia (ASX listed), Implicit Bioscience Pty Ltd, Neurotide Pty Ltd and TetraQ (the commercial arm of Centre of Integrated Preclinical Drug Development).
Professor Istvan Toth is a Chemical Engineer specialized in Medicinal Chemistry. Istvan ARC Australian Professorial Fellow is Chair in Biological Chemistry and Professor of Pharmacy at the University of Queensland. He has an adjunct Group leader appointment at the Institute of molecular Biosciences, UQ as well. His Ph.D. and postdoctoral research was focused on organic synthesis; mainly on reserpine alkaloids and terpenes. Then he changed his research directions towards peptide and carbohydrate chemistry and nowadays he is an internationally recognized expert in drug delivery.In 1994, he was awarded a DSc degree for his work on Drug Delivery. Istvan is also an elected Fellow of RACI and the Queensland Academy of Art and Science.He has also demonstrated track record in research commercialization; Professor Toth is one of the key founders of Alchemia (ASX listed), Implicit Bioscience Pty Ltd, Neurotide Pty Ltd and TetraQ. He is the Editor in Chief of Current Drug Delivery and Drug Delivery Letters; Associate Editor of Medicinal Chemistry; Board Member of Mini Reviews in Medicinal Chemistry, Open Drug Delivery, Open Medicinal Chemistry and Current Patents in Drug Delivery. Professor Toth has over 300 peer-reviewed publications and 43 patents.
- Track 2: Developing Next-Gen Conjugate Vaccines
Track 17: Childhood vaccines
Track 18: Cancer vaccines
Track 20: Delivery Technologies
Track 21: Vaccines Business and Development
Director, Chief Scientific Officer, Gamma Vaccines, Australia
Time : 09.30-09.55
Rodolfo M. Alarcón worked in the areas of infectious disease and translational research for over 10 years and has held positions of increasing responsibility in the Federal Government. He pursued his Ph.D. in Cancer Biology from Stanford University and postdoctoral research at Harvard Medical School. He was a scientist with the Air Force Research Laboratory and is now a Program Officer and a Contracting Officer Representative in the Enteric and Hepatic Diseases Branch within NIH. He currently manages a basic, preclinical, and clinical grant and contract portfolio focused on enteric virus therapeutic and vaccine development.
The overall mission of the Enteric and Hepatic Diseases Branch (EHDB) is to manage and grow vigorous research and development portfolios focused on bacterial and viral pathogens such as Shigella, rotavirus, and noroviruses. To carry out this mission EHDB uses extramural grants and contracts to aid in the development of new and improved interventions for the benefit of public health. Independent investigator initiated grants such as R01s are the predominate funding mechanism for infectious disease focused research, however, to assist academic and industrial developers of vaccines and therapeutics, a series of contracts have been established at the Division of Microbiology and Infectious Diseases (DMID). These contracts encompass a multitude of vaccine preclinical and clinical services. In working with grantees and industry collaborators, our preclinical services contracts are utilized for a vast array of vaccine development services such as manufacture of master and working cell banks and immunogenicity testing. Our Vaccine and Treatment Evaluation Units contract is our primary clinical services mechanism for funding vaccine trials and epidemiological studies. This presentation will highlight our current preclinical and clinical vaccine efforts and development resources for investigators interested in vaccine product development.
University of Genoa, Italy
Time : 09:55-10:20
Gilberto Filaci is Associate Professor of Internal Medicine and vice-director of the Centre of Excellence for Biomedical Research at the University of Genoa. He has published more than 80 papers in reputed journals and has been serving as official reviewer for international journals and research funding organizations. His scientific activity is mainly focused on immunoregulation and on the search for new diagnostic and immunotherapeutic agents (so far he applied for four invention patents). He is in the advisory board of pharmaceutic industries.
Telomerase, the enzyme synthesizing the telomeric regions of chromosomes, is considered a universal tumor associated antigen because expressed by the majority of cancers. The several clinical trials performed adopting telomerase as immunogen confirmed the safety of telomerase vaccination, but raised doubts concerning: a) the immunogenicity of telomerase; b) the capacity of telomerase vaccines of inducing clinical responses. The immunogenicity concerns have been now dispelled by demonstrations that: 1) telomerase is presented by tumor and antigen presenting cells; 2) ex vivo generated telomerase-specific CTL kill efficiently telomerase-expressing tumors; 3) circulating telomerase-specific T cells are present in 90% of cancer patients and, surprisingly, in 100% of healthy individuals, as observed in two our studies. These findings boost the search for a new generation of telomerase vaccines able to overcome the limits of their first generation. In this effort, our group recently completed a phase I/II trial in prostate and renal cancer patients with GX301, a new generation cancer vaccine. This multi-peptidic vaccine includes four telomerase peptides, which bind promiscuously several HLA class I and II alleles allowing the coverage of the majority of HLA haplotypes and the induction of both helper and cytotoxic T cell responses. It also contains two adjuvants with complementary activities, making it able to efficiently activate both innate and adoptive immune responses. The results of a phase I/II trial, showing a 100% rate of telomerase-specific immune responses associated with evidences of clinical responses, suggest that innovative approaches may lead telomerase (and cancer) vaccination to an "age of maturity".
Spruson & Ferguson, Australia
Title: Impact of Myriad Decisions on Patent Eligibility of Biotechnology Inventions in Australia and the US.
Time : 10:35-11:00
Simon Potter completed a PhD for research in the area of virology and genetics at the Westmead Millennium Institute Sydney in 2004. He undertook postdoctoral research at the Pasteur Institute in France from 2004-2006, working in the areas of human immunology and cellular biology. Simon joined Spruson & Ferguson in early 2007 and is a registered patent attorney in Australia and New Zealand. He is also a registered Australian Trademark attorney. Simon became a Principal of the firm in 2012, and has particular expertise in identifying, protecting, and advancing intellectual property rights in the field of biotechnology both in Australia and overseas.
The eligibility of certain biotechnological inventions for patent protection has come under intense scrutiny in recent years, both in Australia and the United States (US). For example, the patent eligibility of biological substances has been subject to judicial review in both countries by virtue of the various Myriad Genetics cases. In the US, the Myriad litigation and other judicial decisions (e.g. Mayo v Promotheus) have culminated in a less favourable environment for applicants seeking patent protection for certain types of biological inventions. In contrast, the Australian courts in considering the Myriad cases have, at least thus far, delivered a favourable outcome for patent applicants in Australia. However, the High Court of Australia (HCA) recently granted special leave to appeal the earlier decision of the Full Federal Court (FFC) on the Myriad cases, a development that raises uncertainty as to the longevity of the FFC’s decision. The HCA is expected to provide its decision in late 2015. This oral presentation will provide an overview of the current positions in Australia and the US relating to the patent eligibility of biotechnological inventions, as relevant to vaccines and other similar technologies.
The University of Queensland, Australia
Time : 11:00-11:25
Associate Professor Neena Mitter, at Queensland Alliance for Agriculture and Food Innovation, the University of Queensland (UQ) is one of Queensland’s leading biotechnologists and has won prestigious awards like Women in Technology Queensland Biotechnologist Award, Queensland International Fellowship and Young Scientist Award by the Prime Minister of India. Her successes include a Gates Foundation grant on ‘BioClay’, a nanoparticle based delivery of RNA silencing for crop protection, which is now further supported by industr https://www.linkedin.com/pub/neena-mitter/10/4ab/13y and government. She is heavily invested in agricultural nanotechnology and currently leads a consortia of scientists from UQ , Washington State University, Zoetis and Department of Agriculture and Fisheries, Queensland to develop ‘Nanovaccines for animal health’.
We have developed a nano-carrier delivery system for vaccines that demonstrates strong adjuvant effects, potential for reducing dose number and elimination of cold chain requirements. The technology was developed to reduce the administration costs of vaccines and to improve compliance, a key factor undermining the effectiveness of multi-dose vaccines. The novel hollow silica vesicles (SV) nano-carriers have a well-controlled diameter in the range 30-70 nm and a thin wall of just a few nanometres perforated by pores of controllable size in the range 6-20 nm. The large internal cavity acts as a high capacity reservoir for biologics such as proteins which are easily loaded through the large pores in the vesicle walls. The carrier vesicles are sized for effective endocytosis and display a strong adjuvant effect, potentially removing the requirement for dedicated adjuvants in a formulation. The SV nano- carrier technology has been demonstrated in mouse trials, initially in an animal vaccine application targeting Bovine viral diarrhoea virus BVDV using the subunit vaccine E2 protein, an immunogenic fragment which is active for prevention of BVDV. Use of the E2/SV formulation significantly increased the humoral as well as cell mediated immune response over the formulation using the standard Quil A adjuvant. We have further shown that vaccination with non-freeze-dried and the freeze-dried E2/SV formulation elicited balanced immune responses for up to 6 months post the final second immunisation. The technology is currently being developed for animal vaccine applications and has the potential for translation to human health.
University of Melbourne, Australia
Time : 11:25-11:50
Julie Bines is the Victor and Loti Smorgon Professor of Paediatrics at the University of Melbourne and a paediatric gastroenterologist at the Royal Children’s Hospital. She leads the Rotavirus Vaccine Group at the Murdoch Childrens Research Institute in the development of RV3-BB, a human neonatal rotavirus vaccine for the prevention of rotavirus disease from birth. She is a member of the ROTA Council and the co-convenor of the International Rotavirus Symposium to be held in Melbourne in 2016.
Rotavirus is the most common cause of severe dehydrating gastroenteritis worldwide, causing about 450,000 deaths per year in children < 5 years of age and hospitalizing millions more. Rotavirus vaccines have been associated with a reduction in rotavirus hospitalisations in low- and high-income countries and a reduction in death in young children in Mexico and Brazil. In 2009, the WHO recommended that all children be vaccinated against rotavirus. Today 78 countries administer rotavirus vaccines in the National Immunisation Program, including some of the world’s poorest countries assisted by GAVI. Rotavirus vaccines have been demonstrated to be highly cost-effective and data is now emerging of the indirect benefits of rotavirus vaccination. Despite these significant achievements there remain some challenges to the success of rotavirus vaccines, including vaccine efficacy in regions with high rates of severe disease, burden on the cold chain, safety concerns and cost. These challenges are the focus of ongoing research and development efforts. The RV3-BB rotavirus vaccine is a human neonatal rotavirus vaccine under development at Murdoch Childrens Research Institute, Australia. RV3-BB is an oral vaccine targeting birth dose administration and has the potential to improve the effectiveness and safety of rotavirus vaccines in low-income countries.
Hilleman Laboratories Pvt. Ltd, India
Title: How promising is the development of a semi-synthetic meningococcal conjugate vaccine? - a case study
Time : 11:50-12:15
Dr. Manoj Kumar, Ph.D. (Bacteriology), presently working as Associate Director, R&D at MSD Wellcome Trust Hilleman Labs is heading the conjugate vaccine research portfolios. In his 15 years of research career, he has worked on several vaccine, biosimilar product and diagnostics development projects. He has 9 patent applications, 11 publications, 2 book chapters, 4 popular articles, 7 gene sequences, 12 national and international awards in his name. He is a contributing scientist on revision of WHO TRS927 Annex 2 for manufacture and evaluation of pneumococcal conjugate vaccines. His focus areas include: New vaccine development; Cost effective vaccine technologies; Developing faster analytical methods, and Technology transfers.
Infection due to Neisseria meningitidis (Men) is the leading cause of bacterial meningitis with high mortality worldwide and significant epidemics in sub-Sharan Africa. Glyco-conjugate and protein based vaccines are currently available against single or combination of meningococcal serogroups. However, most of these vaccines are available at prohibitively high costs and not affordable to people in developing countries who need these vaccines the most. A significant part of the cost of conjugate vaccine production is attributed to the complex steps in production of bacterial capsular polysaccharide (MenPS) and its conjugation to the carrier protein. We have explored an alternative approach to the development of meningococcal conjugate vaccines by organic synthesis of the oligomers of MenPS repeating units for serogroup C, Y, W and X. The synthetic oligomers of serogroup C (sMenC) and X (sMenX) were used for conjugation to tetanus toxoid(TT) by a simple chemistry through an in-built linker. The sMenC-TT conjugates when tested for immunogenicity in the mouse model, were found to elicit IgG and functional antibody titers comparable or better than those elicited by a licensed vaccine. The sMenX-TT conjugate also gave rise to more than 10 fold antibody titers as compared to the vehicle control. The results point to the possibility of developing an affordable semi-synthetic multi-valent meningococcal conjugate vaccine. The simplicity of manufacturing requirements, in-built linker, common conjugation chemistry for all serogroups, least loss of epitopes, high yields and highly defined oligomers/conjugates make the semi-synthetic conjugate vaccine platform an attractive option for use in the developing world.
MRC Laboratories, Tasmania
Title: Non-targeted effects of childhood vaccines: epidemiological evidence and emerging immunological mechanisms
Time : 12:15-12:40
Associate Professor Katie Flanagan is a clinical Associate Professor at the University of Tasmania and leads the Infectious Diseases Service at Launceston General Hospital. She is also an Adjunct Senior Lecturer in the Department of Immunology at Monash University in Melbourne. She obtained a degree in Physiological Sciences from Oxford University in 1988, and her MBBS from the University of London in 1992. She is a UK and Australia accredited Infectious Diseases Physician. She did a PhD in malaria immunology based at Oxford University (1997 - 2000). She was previously Head of Infant Immunology Research at the MRC Laboratories in The Gambia from 2005-11 where she conducted multiple immunological vaccine trials in neonates and infants. Her research aims to understand how the infant immune system develops in response to vaccines and infections encountered in early life, and the impact of aging on immune responses to vaccines, with a particular focus on sex differences in immunity and non-targeted effects of vaccines.
It is now recognised that vaccines administered in infancy can have non-targeted or heterologous effects on the immune system and alter susceptibility to non-vaccine related infections. In the case of BCG and measles vaccines these effects are beneficial leading to decreased susceptibility to infections; while for other vaccines such as the diphtheria, tetanus, pertussis vaccine (DTP) these can be harmful leading to increased infections and all-cause mortality. Intriguingly, female infants are generally more susceptible to non-targeted effects of vaccines than males. The immunological basis for such non-targeted effects are beginning to be teased out, and are likely multifactorial. For BCG vaccination, it has been shown that the vaccine can have epigenetic effects leading to enhanced innate immunity; while DTP vaccine can suppress innate and T cell immunity. The reasons for sex differences include the effects of sex hormones, X- and Y-linked immune response genes and microRNAs. This talk will discuss the epidemiological and immunological evidence for non-targeted effects of vaccines, and describe newly emerging data that support sex-differential heterologous effects of DTP and measles vaccination in infants.
Clinical Network Services (CNS) Pty Ltd, Australia
Time : 13:55-14:20
Mark Reid is the Director of BioDesk and Regulatory Affairs at Clinical Network Services (CNS) Pty Ltd and has a broad background in Regulatory Affairs with his main area of interest being anti-infective drugs and vaccines. Mark is a virologist by training and has worked on nine anti-infective drug programmes and 12 vaccine programmes including genetically modified organism (GMO) vaccines. One vaccine is now registered in Australia, India and Thailand. Prior to working in the pharmaceutical industry, Mark setup a virological laboratory under ISO 17025 (1999) and ISO 9001 (2000) for specialised virology and serology services. Mark has a BSc (hons), MMedSci (drug dev) and MBA. Mark is also a certified member (by examination) of the Regulatory Affairs Professionals Society for both European and US filings.
Key practical steps for moving a vaccine candidate from laboratory grade research material and animal proof of concept data to human clinical trials is discussed. Key considerations include manufacturing considerations (to Good Manufacturing Practice, GMP) and the capacity to make the vaccine at industrial scale with long stability periods; Good Laboratory Practice (GLP) toxicology studies, species selection and study types will be discussed in addition to the design of First in Human studies to demonstrate safety, tolerability and immunogenicity of early vaccine candidates. Key business considerations for the investigator “pitch deck” are also reviewed as the first question asked by large, vaccine companies when considering a new vaccine is: “can this vaccine be sold”.
University of Queensland, Australia
Title: Use of system biology to identify genes associated with enhanced immunogenicity to a skin patch (nanopatch) delivered vaccine
Time : 14:20-14:45
Dr. Germain Fernando completed his PhD at the University of Arizona, USA and postdoctoral studies at the Baylor College of Medicine in Texas, USA. He is now working as a Senior Research Fellow at the Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, Brisbane, Australia, developing needle-free vaccines.
Vaccinations greatly reduce the burden of infectious diseases. The current vaccination methods using the needle and syringe, have a number of drawbacks. Firstly, they require liquid vaccine for delivery, as such, there is a need for cold chain during transportation. Secondly, intradermal (ID) and intramascular (IM) vaccination rely on trained personnel to perform these techniques. Finally, using needle and syringe introduce risks of needle-stick injury as well as the spread of blood-borne diseases. The Nanopatch mitigates these issues. Vaccine dry-coated onto the Nanopatch retains its activity even after six months at 25°C. The Nanopatch is designed to be easily administrable using a hand held applicator with the potential for self-administration. The Nanopatch delivers vaccine to the skin’s viable epidermis and dermis layers. This reduces the possibility of damaging the blood vessels due to the array microprojections measuring only 0.11mm. We have previously shown that the Nanopatch is able to induce similar immune response with ID injection with 1/10th  and IM injection with a 1/100th of the vaccine dose in mice . The Nanopatch has demonstrated to be a more advantageous route of vaccination than the conventional ID and IM, in both immunogenicity and administration. However there is still a need for a broader understanding of the mechanisms that lead to the enhanced immune response induced by the Nanopatch. To approach this question, we used systems biology methods to investigate which genes are up/down regulated at the site of vaccination. Here, I will discuss the Nanopatch molecular profile compared to ID. This study will contribute towards the knowledge for new potent vaccine development and better understanding of the molecular mechanisms of the Nanopatch action. We envisage the outcome will allow Nanopatch technology to translate from murine to larger animal models and ultimately leading into human clinical trials.
QAAFI/Centre for Animal Science, Australia
Title: Immunisation using microspheres of poly glycidyl methacrylate functionalized with MSA-2 peptide to protect cattle from babesiosis
Time : 14:45-15:10
Manuel Rodriguez Valle has a major in Biochemistry and completed his PhD in Genetics in 1995 at The University of Havana, Cuba. From 1986-2005 worked as Postdoctoral and Research at Genetic Engineering and Biotechnology Centre, Cuba where developed a cattle tick vaccine (GavacTM). Currently works as Senior Research Fellow at QAAFI. Research Interests: Genomic, Functional Genomic and Applied to Animal Biotechnology. He has published more than 50 papers in reputed journals.
Babesia bovis is a protozoan parasite transmitted by Rhipicephalus microplus ticks causing significant economic losses and limits cattle production in tropical and subtropical regions of the world. Vaccination with live attenuated parasites is an effective control method that protects susceptible cattle preventing babesiosis outbreaks in areas of enzootic instability, and protects animals raised in tick free zones when transferred into endemic areas. These live Babesia vaccines are usually effective but have a numerous disadvantages including reversion to virulence if transmitted by ticks. Additionally, vaccination is only safe in young bovines (~ 1 year old). The present study developed microspheres with ~1 µM size of poly glycidyl methacrylate (poly-GMA) that were functionalized by Click chemistry methodologies with highly immunogenic and protective B cell epitopes from the B. bovis merozoite surface antigen MSA-2. The peptide-functionalized microspheres were utilized in mouse inmmunisation experiment. Mouse anti-peptide antibodies recognized B. bovis merozoite extracts in ELISA screening. In addition, sera against the peptides inhibited erythrocyte invasion by cultured B. bovis merozoites in vitro. However, cattle immunized with the MSA-2 peptide-microparticles were not protected against challenge with the virulent B. bovis strain (Calliungal). Finally, further studies should be conducted in order to improve the development of a new generation of vaccine(s) against this apicomplexan protozoan parasite.
University of Sydney, Australia
Title: A Novel Quantitative Fluorescence Spectroscopy Method to Estimate the Surfactant-Induced Split Ratio of Influenza Virus
Time : 15:10-15:35
Veysel Kayser is an Associate Professor in the Faculty of Pharmacy at the University of Sydney. He received his Ph.D. from the University of Leeds (UK) and performed post-doctoral research at the Max-Planck Institute (Germany) and at MIT (US). Before joining the University of Sydney, he was a senior scientist at MIT. His research focuses on protein folding and aggregation, development and formulation of biopharmaceuticals (mAbs and vaccines), molecular engineering for biotherapeutics, virus and vaccine characterization. He has published numerous papers on the subject, supervised HDR students, and serves as a reviewer for various journals.
Most of the seasonal flu vaccines are produced after chemical inactivation and non-ionic surfactant treatment of the viruses with an aim of producing a vaccine product that has a low level of reactogenicity with high potency. Surfactants cause viruses to ‘split’ due to the membrane solubilisation and they further stabilize unbound membrane proteins. Consequently, this ‘splitting’ process affects the formulation stability and potency of flu vaccines greatly. Hence, finding the ideal splitting conditions and being able to estimate the split ratio quantitatively is of utmost importance for rapid preparation of flu vaccines. Here, we present a quantitative method, employing both steady-state and time-resolved fluorescence spectroscopy, to estimate the split ratio of flu virus following surfactant treatment. A lipophilic fluorescent dye was used to probe the molecular interactions and track changes in micro-environments. The fluorescence spectra of the dye shift towards the red side of the spectrum after the surfactant is added, suggesting disappearance of hydrophobic environments due to membrane solubilization. Results from both methods correlated well and showed that there are three distinct molecular environments with emission maximums at ~589, 630 and 670 nm and with fluorescence lifetimes of 4.45, 2.21 and 0.650 ns, respectively. Subsequently, we calculated the split-ratio of the virus using the percentage of dye in different micro-environments from both data sets. This study forms the basis of an in situ method to quantify split viruses during vaccine manufacturing and will facilitate the rapid development of the flu vaccine in a more controlled manner.