5^th Asia Pacific Global Summit and Expo on Vaccines & Vaccination July 27-29, 2015 Brisbane, Australia

Biography:

Denise Doolan is a molecular immunologist who heads the Molecular Vaccinology Laboratory at the QIMR Berghofer Medical Research Institute. She is an NHMRC Principal Research Fellow and was previously a Pfizer Australia Senior Research Fellow. Her research investigates the molecular basis of immunity, with a focus on malaria and rational vaccine development. Her research program encompasses core themes of: (i) immune mechanisms; (ii) antigen and epitope discovery from genomic sequence data; and (iii) molecular vaccine technologies. She has published over 120 research articles, is an inventor on a number of patents, and has been a consultant for a number of biotechnology companies.

Abstract:

Vaccines are the most efficient health care intervention for global public health but vaccines against many diseases caused by complex pathogens are still not available despite intense research. A significant advance of the past decade has been the elucidation of the genome, proteome and transcriptome of many pathogens. These datasets provide the foundation for genome-based approaches to identify target antigens for rational vaccine design. Using malaria as a model, we are pursuing a multi-pronged approach using technology platforms including protein microarrays, high throughput protein production, and epitope prediction algorithms, with specimens from humans, or animals naturally or experimentally exposed to malaria. We have established that T cell and antibody responses to the Plasmodium parasite are broadly distributed throughout the proteome, and have identified many novel antigens that are more immunogenic than antigens currently considered as high priority vaccine antigens. Importantly, the subsets of antigens preferentially recognized by T cells are distinct from the subset targeted by antibodies. We have further integrated and analyzed our comprehensive antibody and T cell datasets to identify specific features associated with antibody or T cell immune reactivity. Our data significantly expand our knowledge base of targets of host-parasite immunity and suggest that distinct vaccine approaches and antigen targets are required depending on whether antibodies or T cells are the desired vaccination outcome. Such genome-based vaccine approaches may overcome the problem of poorly efficacious vaccines that has plagued vaccine developers for many years.

Biography:

Filip Dubovsky is a Vice President in Clinical Biologics and the Therapeutic Area Head for Infectious Disease and Vaccines at MedImmune/AstraZeneca. He has a BA in cell biology from Cornell University, a MD from the University of Alabama and a MPH from John’s Hopkins University. He completed his pediatric training at Stanford University, Pediatric Infectious Disease Fellowship at the Center for Vaccine Development at the University of Maryland and Preventive Medicine training at Johns Hopkins University.

Abstract:

Maternal vaccination has advanced as an approach to protect newborns against neonatal diseases. An alternative to maternal vaccination is passive vaccination using monoclonal antibodies (mAbs). Advances in mAb potency, extended half-life technology and manufacturing techniques allows for the development of monoclonal antibodies that can be used as passive vaccines in infants. MEDI8897 is a passive RSV vaccine for preterm and term infants. The optimization of a human derived mAb led to a 200-fold improvement of in vitro potency compared to palivizumab. Mutations in the Fc region have enabled a 3-fold increase in antibody half-life compared to standard IgG. In combination, these advances have resulted in a mAb that can be used as a passive vaccine to protect infants through an entire RSV transmission season with a single fixed intramuscular dose. MEDI8897 was evaluated in healthy adult volunteers (N=136). A range of intravenous and intramuscular doses were evaluated: the safety profile was favorable, and the mean half-life was extended to 67-80 days across all dosage groups. Anti-drug antibody was low and did not impact the pharmacokinetics. The safety and pharmacokinetic profile supported advancement of MEDI8897 into infant clinical studies. In temperate climates with a discreet RSV season, MEDI8897 can be used at the beginning of respiratory viral season to protect infants entering their first RSV season. In tropical climates, where the RSV transmission can be prolonged, MEDI8897 can be used as a birth-dose to protect newborns for the first six months of life where the risk of severe disease is greatest

Biography:

Carmen Alvarez-Dominguez has completed her Ph.D at the age of 29 years from Universidad Autonoma de Madrid and postdoctoral studies from Washington University School of Medicine on Small GTPases role in Listeria monocytogenes phagocytosis. She is the director of the Group on Genomics, Proteomics and Vaccines at the Research Institute Marqués de Valdecilla (IDIVAL) in Santander, Spain. She has published more than 26 papers in reputed journals and serving as an editorial board member of Microbes and Infection and OMICS. She also is coauthor of the patent: Immunogenic peptides against Listeria and Mycobacterium, antibodies and their uses with reference PCT/ES2007/070144.

Abstract:

Susceptible and resistant mice to listeriosis are convenient models to examine vaccines efficiency since they mimic human diversity. Dendritic cells (DC) vaccines loaded with immunogeneic peptides are powerful tools for the vaccination against intracellular bacteria. To produce a vaccine against the human bacterial pathogen, Listeria monocytogenes, we assessed DC loaded with immunogenic listeriolysin O (LLO) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) peptides. Our approach consisted on examining DC-LLO or DC-GAPDH vaccines coupled with peptides with different binding capacities to MHC molecules in susceptible or resistant mice. DC-GAPDH1-22 vaccines that contained weak binding sequences to IAb and IAd MHC class II molecules and medium binding sequences to H-2Kb and H-2Kd MHC class I molecules, provided the best protection to listeriosis in susceptible and resistant mice. DC-LLO91-99 vaccines loaded with a strong peptide binder to H-2Kd but weak binder to H-2Kb MHC class I molecules, conferred better protection than DC-LLO296-304 vaccines loaded exclusively with a strong peptide binder to H-2Kb. DC-LLO190-201, DC-LLO189-200 and DC-LLO189-201 vaccines loaded exclusively with weak peptide binders to IAb and IAd MHC class II molecules, respectively, presented no significant protection. Enhanced protection in listeriosis correlated with increased splenic CD8+ DC, enhanced IL-12 and expansion of Listeria antigen specific CD8+ and CD4+ T cells producing IFN-. DC-GAPDH1-22 vaccines that combine any type of CD8+ epitopes and CD4+ weak binder epitopes conferred higher protection to listeriosis in susceptible and resistant mice, than DC-LLO91-99 or DC-LLO296-304 vaccines that include exclusively CD8+ epitopes. DC-GAPDH1-22 vaccines could be an effective vaccine for prophylactic protection against human listeriosis in susceptible and resistant individuals.

Biography:

A/Prof Mahony received his PhD in molecular biology from James Cook University. He is a molecular virologist who joined the University of Queensland in 2010 after 15 years working with the AgriScience Queensland. A/Prof Mahony's research interests include the characterisation of animal pathogens and how they interact with their respective hosts. By better understanding disease development his research is improving disease prevention and management in livestock industries. His research has been published in international journals and has been subjected to patenting. A/Prof Mahony currently leads research projects developing vaccines for bovine respiratory disease and cattle ticks.

Abstract:

Bovine respiratory disease (BRD) is the most important cause of morbidly and mortality in intensively finished cattle in the world. The total economic losses attributed to BRD have been estimated to exceed US$1 billion annually. The disease has a complex aetiology involving a range of viral and bacterial pathogens, animal factors and environmental conditions all contributing to BRD development. It has been demonstrated that prior exposure to specific pathogens can reduce the risk of cattle developing BRD which suggests that vaccines could play a role in ameliorating the impacts of this disease. However the range of pathogens implicated in BRD presents significant challenges in the development of effective vaccines. Currently there are four viruses and three bacteria commonly implicated in BRD development. Furthermore the meaningful assessment of vaccine efficacy in the context of such complex disease aetiology can also be problematic. To address these issues the development of multivalent live viral vaccines has been undertaken using a bovine herpesvirus 1 infectious clone to deliver antigens from other BRD pathogens. In addition the capacity of these prototype vaccines to protect cattle from BRD are being assessed in biphasic multi-pathogen challenge models to more accurately assess field efficacy. The progress towards achieving these goals and ultimately improved control of BRD will be discussed.

Biography:

Helle Bielefeldt-Ohmann is a veterinary pathologist focusing on the pathogenesis of infectious diseases, in particular zoonotic diseases and virus infections causing neuropathology. Bielefeldt-Ohmann is championing the use of ‘natural animal models’ for studies of infectious diseases of importance to both human and animal health as part of the concept “One World Medicine”. Her current research activities are mainly focused on the pathogenesis of flavivirus-induced encephalitis and foetal encephalopathy, melioidosis and tuberculosis. Other infectious diseases of interest include rhadinovirus induced neoplasia and vasculopathy.

Abstract:

In 2011, following severe flooding in Eastern Australia, an unprecedented epidemic of equine encephalitis occurred in South-Eastern Australia, caused by Murray Valley encephalitis virus (MVEV) and a new variant strain of Kunjin virus, a subtype of West Nile virus (WNVKUN). This prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived Japanese encephalitis virus (JEV) vaccine (JE-ADVAXTM) could be used in horses, including pregnant mares and foals, to not only induce immunity to JEV, but also elicit cross-protective antibodies against MVEV and WNVKUN. Foals, 74-152 days old, received two injections of JE-ADVAXTM. The vaccine was safe and well-tolerated and induced a strong JEV-neutralizing antibody response in all foals. MVEV and WNVKUN antibody cross-reactivity was seen in 33% and 42% of the immunized foals, respectively. JE-ADVAXTM was also safe and well-tolerated in pregnant mares and induced high JEV-neutralizing titers. The neutralizing activity was passively transferred to their foals via colostrum. Foals that acquired passive immunity to JEV via maternal antibodies then were immunized with JE-ADVAXTM at 36-83 days of age, showed evidence of maternal antibody interference with low peak antibody titers post-immunization when compared to immunized foals of JEV-naïve dams. Nevertheless, when given a single JE-ADVAXTM booster immunization as yearlings, these animals developed a rapid and robust JEV-neutralizing antibody response, indicating that they were successfully primed to JEV when immunized as foals, despite the presence of maternal antibodies. Overall, JE-ADVAXTM appears safe and well-tolerated in pregnant mares and young foals and induces protective levels of JEV neutralizing antibodies with partial cross-neutralization of MVEV and WNVKUN.

Biography:

Yuzhang Wu has completed his Ph.D for Immunology at the age of 29 years from Third Military Medical University School of Medicine. He is the director of the Institute of Immunology, PLA, the Chair of National Engineering Lab for Vaccine Development of China and National Center for Immunoproducts Research and Development of China. He has published more than 150 papers in reputed journals, applied for 75 international and national invention patents, among which 43 has been approved; and has gained 2 item of Computer software copyright. He is serving as chief-editor of Immunological Journal

Abstract:

As chronic diseases, such as tumor, persistent infections, autoimmune diseases, cognitive diseases and metabolic disorders, are the main health problems at present for human, there is a clear need for postexposure vaccines, most of which are therapeutic. To date few postexposure vaccines have been licensed to industry, although large amount of studies had been conducted in the past 20 years. There is a clear indication of the era of transformational development of vaccine. For postexposure vaccine development, we need clear target, novel strategy, and new technologies in vaccine design, adjuvant, and delivery systems. From the view of immunology, there are several challenges: Heterologous immunity, narrowed TCR repertoire, individual TCR usage, cross and pathologic reactivity, antigen load and heterologous immunity, immune deviation. This talk will summarize recent achievements in post-exposure vaccinology development and insight into challenges in immunology.

Biography:

Abstract:

The global persistence of tuberculosis (TB) epidemic and the current spread of drug resistant M. tuberculosis (Mtb) strains have stimulated an unprecedented rush to develop novel efficient vaccines. An important strategy toward this goal remains improving the efficacy of current BCG vaccine based upon its remarkable safety record during almost 100 year of massive human immunization. Current strategies to improve BCG attempt to over-express genes encoding specific Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA, in particular antibiotic resistant genes, into human cells and tissues. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and to a fusion of Mtb antigens ESAT6/TB10.4 were generated and tested for immunogenicity functions. We found that modified BCG strains displaying ovalbumin antigen or ESAT6/TB10.4 induce an immune response in the mouse similar to that induced by BCG genetically expressing the same antigens. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Biography:

Ken Beagley completed his PhD at the University of Otago and is a Professor of Immunology and Deputy Director at the Institute of Health and Biomedical Innovation at Queensland University of Technology. He has worked in the area of mucosal and reproductive immunology for the past 25 years at the University of Alabama at Birmingham and the University of Newcastle prior to moving to QUT. He has over 200 publications, is on the editorial boards of Mucosal Immunology, Vaccine and Journal of Reproductive Immunology and is the current president of the Society for Mucosal Immunology.

Abstract:

Chlamydia trachomatis is the most common STI in Australia. Current antibiotic therapies have not halted the increased incidence (4-fold in the past decade) and no vaccine is currently available. Infection-induced inflammation causes pelvic inflammatory disease, ectopic pregnancy and infertility in women, the most expensive outcomes of chlamydial infection and may also compromise male fertility. Protective immunity against Chlamydia requires a strong mucosal Th1 response together with mucosal antibodies. We have used a mouse model to evaluate different adjuvants and mucosal routes of vaccine delivery, combined with the major outer membrane protein antigen (MOMP) in order to elicit protection against both infection and inflammatory disease of the female reproductive tract. The magnitude and duration of infection was reduced by intranasal, sublingual and transcutaneous vaccine delivery of MOMP with different adjuvants, however intranasal immunisation with either Iscomatrix® or a combination cholera toxin/CpG (CT/CpG) adjuvant provided the greatest protection against infection. Interestingly, sublingual immunisation using the CTA1-DD adjuvant plus MOMP protected against inflammatory disease without preventing ascending infection while intranasal immunisation with the CT/CpG adjuvant prevented ascending infection but not the development of inflammatory disease. Intranasal immunisation of mice with a combination of antigens, selected from different stages of the chlamydial developmental cycle, combined with Iscomatrix® protected mice against both ascending infection and inflammatory oviduct damage. Our data suggest that chlamydial disease is independent of the infectious burden and that it is possible to develop vaccines that protect against inflammatory damage even in the absence of sterilising immunity.

Biography:

Prof Suhrbier is a Group Leader at the Inflammation Biology, QIMR B, Australia www.qimrberghofer.edu.au/page/Lab/Inflammation_Biology/. He has 140 international peer reviewed publications, 5794 citations (H index 44) and 17 patents, 6 cover products, 2 are in phase II trials. Publications can be found on http://scholar.google.com.au/citations?hl=en&user=KxKWgxwAAAAJ&view_op=list_works&sortby=pubdate.

Abstract:

Chikungunya virus is a mosquito borne alphavirus (related to the Australian Ross River virus) which has recently re-emerged to produce the largest epidemic ever recorded for this virus, with recent outbreaks in the Caribbean (with an estimated 1 million cases) and in Papua New Guinea and the Pacific Islands. The virus produces a predominantly rheumatic disease, with acute and chronic polyarthritis/polyarthralgia the dominate symptom. A range of vaccines have been developed, with neutralising antibodies against the E1/E2 heterotrimeric surface glycoproteins appearing to be sufficient for protection against viraemia and disease. Although correlates of protection appear clear, the pernicious nature of outbreaks presents a major hurdle for commercial vaccine development. Epidemics of chikungunya virus disease have emerged every 2-50 years, with all continents (aside from Antarctica) affected by one or more outbreak; such epidemiology clearly complicates logistics associated with vaccine testing and deployment 1. The main disease burden is arguably the chronic rheumatic disease, which can last months, occasionally over a year. Chronic disease appears to be due to the persistence of viral RNA and protein in joint tissues, with macrophages believed to be the cell type involved 2. Why the normally robust host immune response is unable to clear the virus is unclear. Whether therapeutic vaccines might help clear persistent virus is also unclear. References: 1. Suhrbier et al. 2012. Arthritogenic alphaviruses - an overview. Nat Rev Rheumatol. 8(7):420-9. 2. Poo et al. 2014. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. PLoS Negl Trop Dis. 8(12):e3354

Biography:

Alexander Khromykh received his BSc degree in Physiology from the Tomsk State University, Russia, and his PhD degree in Molecular Virology from the State Centre for Virology and Biotechnology "Vector”, Russia. He worked as Postdoctoral Fellow at the University of Ottawa in Canada. He then joined Sir Albert Sakzewski Virus Research Centre in Brisbane in 1992 and became a laboratory Head in 2001. He was awarded NH&MRC Senior Research Fellowship in 2004 and moved his laboratory to St Luica campus in 2005 to take an appointment with SCMB. He was the founding Director of the SCMB’s Centre for Infectious Disease Research and is currently the Deputy Director of the Australian Infectious Diseases Research Centre, an NH&MRC Senior Research Fellow and Professor of Virology at SCMB.

Abstract:

Recent unprecendented outbreak of Ebola virus (EBOV) in West Africa which reportedtly infected more than 27,000 people and killed more than 11,000 of them has prompted an urgent need for vaccine. Although a number of EBOV vaccine candidates have been developed and some of them are currently undergoing clinical trials, none of them have yet been approved. We have been developing EBOV vaccine candidate based on self-replicating RNA (replicon) of naturally attenuated strain of West Nile virus, Kunjin (KUN). As an antigen we use glycopprotein GP from EBOV Zaire strain. KUN-GP replicon RNA was packaged into virus-like particles (VLPs) by KUN structural proteins produced in a packaging cell line. D637L mutant of GP with enhanced shedding produced less cytopathicity than wt GP during VLP preparation and allowed generation of higher VLP titres. Two immunizations of guniea pigs with 5 x 106 KUN-GP VLPs using either wt GP or D637L mutant GP resulted in up to 85% protection against challenge with 200 LD50 of guinea pig-adapted EBOV. Further vaccine efficacy studies were performed in African green monkeys. Four anilams were vaccinated twice with 109 KUN-GP D637L VLPs with 4 week interval and 3 weeks after the second immunization they were challenged with 600 pfu of Zaire EBOV. Three animals were completely protected against EBOV challenge, while one vaccinated animal and the control animal died from infection. We suggest that KUN replicon VLPs encoding EBOV GP/D637L represent a viable EBOV vaccine candidate.

Biography:

Kartika Senjarini has completed his PhD (Dr. rer. nat) at the age of 32 years from The University of Rostock – Germany. She had the opportunity to do postdoctoral studies at The University of Kassel, Germany as well as at International Vaccine Institute, South Korea. Apart from her responsibility as principle investigator in the Transmission Blocking Vaccine’s Research Group at her Department, she is currently also appointed as Head of Biology Department, Faculty of Mathematic & Natural Sciences, The University of Jember Indonesia.

Abstract:

Dengue Fever (DF) Virus-based Vaccine development showed a relatively slow progress because it should induce protection against the 4 serotypes of Dengue Viruses and there is a very limited adequate animal model for dengue virus infection. In the last decade, new approach in vaccine development for arthropode-borne diseases is using salivary vector components. This approach based on hyphotesis that arthropode vectors saliva contains vasomodulator and imunomodulator proteins that could enhance pathogen infection. Therefore, it should be possible to control pathogen transmission by vaccinating the host against the molecule(s) in saliva that potentiate the infection, thereby blocking the enhancing effects of saliva and thus preventing the pathogen from establishing infection in the host (Transmission Blocking Vaccine, TBV). However, specific component as a potential target for TBV in Aedes aegypti, as major vector for DF has not yet been identified so far. This paper wanted to elaborate the immunogenic components from Salivary Gland (SG) of Aedes aegypti as potential immunomodulatory protein. We have characterized 2 immunogenic proteins that are only recognized by healthy people living in endemic area and not by people from non-endemic area. They have molecular weight of 31 & 56 kD. Further molecular characterization by Mass-Spectrophotometry of those proteins showed that 31 kDa and dan 56 kDa have high similarity with D7-Protein Family (Odorant Binding Protein) & Apyrase, respectively. These proteins have very important role in vector blood feeding process. This also supported by the strong immunogenicity of 31 kDa against human sera in healthy people as well as Dengue patients. The apyrase activity of 56 kD protein has also been proven in this research.

Biography:

Associate Professor Fiona Russell is a paediatrician with qualifications in public health and epidemiology. She completed her PhD evaluating alternative pneumococcal vaccination schedules in infants in Fiji. The findings informed the pneumococcal conjugate vaccine (PCV) schedules in the latest WHO PCV position paper. She was awarded both the Chancellor and Dean's Prize for PhD Excellence by The University of Melbourne. She has undertaken consultancies for WHO, UNICEF, and Australian Aid in the Asia-Pacific region, and Africa on the disease burden of vaccine preventable diseases, new vaccine introduction, and maternal and child health policies to reduce child mortality and improve maternal health.

Abstract:

Pneumonia is the commonest reason why child die worldwide. It is estimated that one-third of all pneumonia deaths are due to the pneumococcus. Few countries in the Aisa-Pacific region have introduced pneumococcal conjugate vaccine (PCV) and there are few data from this region on the direct or indirect effects of PCV. In this study in Lao PDR, PNG, and Mongolia we will assess the direct and indirect effects of PCV13 on the nasopharyngeal (NP) pneumococcal carriage of children hospitalised with acute respiratory infection. Following PCV13 introduction, a reduction in PCV13 serotype NP carriage is likely to translate into a reduction in pneumococcal disease, and be a marker of direct and indirect immunity. We will use NP carriage surveillance amongst children with acute respiratory infection to estimate the PCV13 coverage required to demonstrate direct and indirect immunity by showing a sustained decline in PCV13 serotype carriage. This study will demonstrate how carriage surveillance in children with pneumonia can be used to estimate the PCV coverage required to show evidence of herd immunity, and monitor the vaccine’s impact on carriage, and thereby provide information for national planners to maximise the effectiveness of their immunisation programs.

Biography:

Suzanne Elliott is the Operations Manager, Chief Scientific Officer and Deputy CEO of Q-Pharm, a Brisbane-based clinical trials company. She has a PhD in molecular oncology from QUT/ Mater Hospital and a post-doctoral career in developing a prototypic vaccine for Glandular Fever with the QIMR Berghofer Eptein Barr Virus group. Subsequent roles at Vaccine Solutions and as the QIMR Berghofer Regulatory Affairs Manager, involved immunotherapy trials for post-transplant lymphoproliferative disease, Hodgkin’s Disease, malaria, prostate cancer and melanoma. Suzanne has qualifications in Drug Development from the University of New South Wales and is an accredited Research Trainer in Good Clinical Practice. Currently the Q-Pharm Scientific and Operations Manager she has responsibility for oversight of ‘all of company’ clinical trial project management and with special interests in early phase adaptive drug design, malaria challenge studies, vaccine studies and research ethics.

Abstract:

Clinical trials are essential for the development of new preventative and therapeutic vaccines in infectious diseases and other therapeutic areas. Trial designs vary based on the nature of the disease; the intended population; the phase of development; the frequency of prime and boost doses; and the length of time associated with follow up activity. Vaccine trial participation is affected by external factors such as the constant community challenge to partake in routine vaccination schedules, and social media commentary by pro- and anti-vaccination advocates, and educational programs on the consequences of non-vaccination. Q-Pharm has undertaken 23 vaccination trials over 13 years. The majority of these trials have been in healthy volunteers for preventative vaccines, with some now registered in Australia and the USA. Recruitability and retention of participants has been impacted by the frequency and timing of prime and boost vaccinations and the duration of follow up. Realistic assessment and understanding of these factors needs to be considered by all parties involved, for early and accurate estimation of participant withdrawal rates and collection of valid data. In Australia, clinical trials involving seasonal vaccines, such as influenza, need to commence early enough to allow immunological responses to be completed before the Southern hemisphere immunisation schedules begin in March/April. Data will be presented that supports our recommendations for establishment of appropriate eligibility and on-trial demands of participants that will enhance recruitment and retention.

Biography:

A/Prof Ala Lew-Tabor joined QAAFI’s Centre for Animal Science in October 2010, after 18 years of conducting research projects with the Queensland Government. She obtained her PhD from The University of Queensland’s Tropical Health Program undertaking molecular analyses of the human and animal pathogen Burkholderia pseudomallei. Post-doctoral research has included genomic studies to develop new vaccines and diagnostic tests to combat beef cattle diseases in Northern Australia. In 2007, A/Prof Lew-Tabor was appointed Adjunct Associate Professor at Murdoch University’s Centre for Comparative Genomics. In 2008, A/Prof Lew-Tabor was the recipient of Qld’s Smart Women Smart State Award for Women in Community/Public Sector- Science Category. In 2013, A/Prof Lew-Tabor was invited to present at the International Symposium for Ticks and Tick Borne Diseases in Brazil, and to participate in the Bill and Melinda Gates Foundation’s ‘Agriculture Research Connections- Livestock’ workshop in Kenya.

Abstract:

Tropical and sub-tropical cattle industries worldwide are threatened by the Rhipicephalus microplus species complex (cattle ticks) with losses due to infestations estimated at $US2.5b annually. Rising tick acaricide resistance and the variable success of Bm86 gut antigen vaccines has diminished options for tick control. Researchers world-wide continue to assess new tick antigens which could potentially protect cattle from different tick species from all relevant geographic locations. A seven year research program undertook a bioinformatics genomics approach to identify putative cattle tick vaccine antigens. This was experimental due to the lack of a complete genome sequence with access to an EST sequence database. Protein databases were screened for domains described as secreted, extracellular and/or transmembrane. R. microplus ESTs with these identified domains were selected for further study. Gene discovery (subtraction hybridization, microarray screening) was also undertaken to identify novel transcripts associated with different tick stages including ticks collected from tick resistant breeds of cattle. Approximately 400 ESTs were subsequently selected for further study. After stringent bioinformatics and localisation analysis using quantitative RT-PCR, the list was reduced to 250 candidates. At this stage, B cell epitope predictions (antibody binding) led to the in vitro screening of over 700 synthetic peptides to identify those recognized by tick resistant cattle. Corresponding antibodies were fed to ticks in vitro to identify 24 antigens producing strong anti-tick effects. Cattle tick challenge trials have yielded 87% protection using a mixture of antigens with on-going research identifying individual antigens with strong anti-tick effects in vivo.

Biography:

Pr. Didier Betbeder has 20 years experience in drug delivery using colloids, ranging from basic research to clinical studies. He has extensive experience in Nanomedicine, and in particular of innovative nanoparticulate for developing prophylactic and therapeutic vaccines. With Biovector therapeutics, nasal flu vaccine formulations based on nanoparticles have been clinically trailed in collaboration with BioChem Pharma, SmithKline Beecham and Chiron. He has been a Professor at the University of Artois and Lille 2 since 2001, his research focusing on drug delivery across biological barriers using nanoparticles. He was president of the French control release society from 2004-8, and has over 60 international publications and 21 patents to his name.

Abstract:

Nanoparticles can be used to deliver antigens to immune cells, therefore increasing their immunogenicity. A better knowledge of their mechanisms of interaction with cells and the biological fluids is necessary to fully understand their potential as delivery systems of antigens. Most of pathogens invade our organism using the mucosal route, therefore it is of interest of mimicking infection in order to elicit a protective immunity against infection. We used nanoparticles made from starch hydrolysate (1), these nanoparticles were loaded with toxoplasma gondii antigens. After intra-nasal administration we observed that they deliver these antigens in airways and are capable of eliciting humoral and cellular responses without the use of adjuvant. A challenge study in comparison of cholera toxin used as adjuvant showed that only mice vaccinated with the nanoparticles were protected (2). This lecture will give an overview of the mechanisms implied using nanoparticles to deliver antigens to the immune cells using the nasal route and will emphasize the interest of developing nanoparticulate carriers. (1) Dombu et al, Biomaterials, 2012 (2) Dimier-Poisson et al, Biomaterials, 2015

Biography:

Charani Ranasinghe completed her PhD from University of Western Australia. She is the Group Leader of the Molecular Mucosal Vaccine Immunology Group at the JCSMR, Australian National University. She was the first to discover that IL-13 plays an important role in modulating CD8 T cell avidity in a vaccine route dependent manner. Her team has recently developed two novel IL-4R antagonist and IL-13Ra2 adjuvanted vaccine platforms that can induce high quality systemic/ Mucosal CD8 T and B cell immunity.

Abstract:

We have shown that the efficacy of a heterologous, poxvirus prime-boost immunization is strongly influenced by the cytokine milieu at the priming vaccination site, where endogenous IL-4/IL-13 is detrimental to the quality of the HIV specific CD8 T cells induced. We have recently developed two novel HIV vaccines that co-express i) IL-13R2 which can transiently inhibit IL-13 activity, and ii) an IL-4R antagonist that can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 activity at the vaccination site. Following intranasal/intramuscular recombinant fowl pox prime, recombinant Modified Vaccinia Ankara virus booster followed by an gp140 Env protein booster these vaccines were able to induced not only high avidity poly-functional mucosal/systemic gag-specific CD8 T cell immunity but also B cell immunity compared to the unadjuvanted vaccine strategy. Whilst IL-13R2 adjuvanted strategy only induced p55gag-specific IgG1 antibodies, the IL-4R antagonist vaccine was able to induce excellent long-lived p55gag-specific IgG1 and IgG2a antibody differentiation. Moreover, following 3-6 weeks post Env protein booster vaccination only the 13R2 adjuvanted strategy, was able to induce elevated env-IgG1 antibody responses. But, at 16-20 weeks both novel vaccines were able to induce elevated env-specific IgG1 antibody responses of high avidity. Collectively, the IL-4R antagonist adjuvanted vaccine strategy was able to induce excellent triple action CD8 T and B cell (gag & env) immunity, similar to HIV elite controllers and the responders in the RV144 trail, which offer good promise for a future HIV-1 vaccine. This strategy also has high potential as a platform technology against may other chronic mucosal pathogens.

Biography:

Bernd Rehm received his MSc (1991), PhD (1993), Postdoctoral Associate (1994) from Ruhr-University of Bochum, Germany; DFG Postdoctoral and Research Grant Fellow (1994-96) from University of British Columbia, Canada; Habilitation in Microbiology (1996-2001), Research Group Leader (2001-2003) University of Münster, Germany; Associate Professor (2004-2005) Massey University, New Zealand

Abstract:

A novel polyester particle technology platform was developed by harnessing the natural capacity of bacteria to produce spherical polyester inclusions ranging in size from 50-1000 nm. These polyester particles are formed within the bacterial cell mediated by the enzyme, polyester synthase. The polyester synthase covers the surface of the polyester beads and has been extensively engineered to incorporate proteins of interest such as enzymes, binding domains and antigens. Here the focus will be on recombinant production of tailor-made polyester beads displaying antigens of interest. A bioprocess has been developed for industrial production of these beads. The use of antigens associated with particles in a size range mimicking infectious viruses and bacteria offers advantages over soluble antigens such as facilitated uptake by antigen-presenting cells (APCs), depot formation as well as co-delivery of antigens and immunomodulatory compounds to the same APC potentially controlling the type of immune response. Besides its use as particulate antigen, diagnostic applications, such as e.g. TB skin test reagent, are currently being developed. This new technology offers an unprecedented design space accompanied with accelerated prototype development. Genetic engineering is applied to express hybrid genes encoding fusions of the polyester synthase with antigen(s). Antigen examples are the hepatitis C virus core (HCc) antigen, various TB antigens (ESAT6, CFP10, Rv3615c, Ag85A) and antigens from Streptococcus pneumoniae and Neisseria meningitidis. The immune response induced by this antigen-bead delivery system was compared to that induced by vaccination with only the soluble antigen. Antigen displaying beads were safe and stimulated an antigen-specific type 1 and 2 immune response resulting in protective immunity. In addition a highly specific TB skin test reagent was developed which shows promise in clinical trials. Antigen-displaying polyester beads manufactured by recombinant bacteria could serve as safe and efficient particulate vaccines as well as show promise for diagnostic applications.

Biography:

Nirmal Marsini received his Bachelor’s degree in pharmacy from Tribhuvan University, (2009) and Master’s degree in pharmaceutical sciences (2012) from Yeungnam University, South Korea under Korean government scholarship specializing in formulation development. Currently, he is a 3rd year PhD student at The University of Queensland in Professor Istvan Toth’s group under IPRS and APA scholarships. His PhD project is focused on developing oral vaccine delivery system for peptide-based antigens. He was a He has also published 19 original papers in reputed pharmaceutical journals including 5 first author papers.

Abstract:

The aim of our project is to develop a novel oral nano-vaccine delivery system against group A streptococcus (GAS) by encapsulating lipid core peptide (LCP) antigens into the liposomes. We synthesized the LCP construct by attaching C-16 lipoamino acids (Toll-like receptor-2 agonist) with J-14 (B-cell epitope derived from GAS M-protein) and P25(universal CD4+ T-helper epitope) using microwave assisted solid-phase peptide synthesis. The optimized LCP-loaded liposome formulations were prepared and their surface were coated with oppositely charged polyelectrolytes [negatively charged sodium alginate and positively charged trimethyl chitosan (TMC) and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Loading efficiency of the LCP-loaded formulations was approximately 80%. DLS and TEM measurements showed spherical monodisperse particles before and after three layers coating with alginate-chitosan-alginate with final size of ~165 nm and ~195 nm, respectively. Positively-charged formulations (LCP-loaded liposomes and double-layered TMC-coated liposomes) had a significant uptake by dendritic cells and macrophages compared to negatively-charged single and triple-layered liposomes. Developed formulations showed an enhanced colloidal stability of liposomes in simulated gastric and intestinal fluid. In vivo oral immunization studies in Swiss outbred mice with double-layered TMC-alginate chitosan-coated liposomes showed higher J-14 specific mucosal IgA and systemic IgG production in the mucosal fluids and serum, respectively as compared to positive controls. Our findings are an important step to towards overcoming the hurdles associated with the development of oral peptide-based vaccines. Taken together, our results suggest that layer-by-layer engineered nano-architecture formulations as a promising novel strategy for oral delivery of lipopeptide-based vaccines.

Biography:

Sharareh Eskandari is pharmacist and has completed his PhD from Isfahan University of Medical Science in pharmaceutics. She is PhD candidate in medicinal chemistry and vaccine delivery at the University of Queensland, School of Chemistry and Molecular Bioscience. She published 8 papers in reputed journals, one eBook chapter in liposomal drug delivery and had been served as responsible pharmacist in pharmaceutical industry.

Abstract:

Adjuvant development is crucially important area of research for improving subunit vaccines. It is important to understand the impact of physicochemical properties of vaccine on immune response to fulfil development of a delivery system with robust protection against infection and tumour. Here, we synthesised a library of lipopeptide (LP) vaccine constructs to contain an asymmetrical arrangement of peptide epitopes (OVA CD4 and OVA CD8) to determine the optimal architecture for stimulation of a potent cell mediated response. C12 or C16 lipoamino acids were included in different locations of the constructs. The constructs were self-assembled in PBS and characterised. C57BL/6 mice were immunised with vaccine constructs following adoptive transfer of congenic (CD45.1) ovalbumin specific OT-I and OT-II T cells. Frequency of proliferation of OT-I and OT-II cells in naïve mice were determined using FACS analysis. Then, the effector function of activated OT-I cells in response to the vaccine constructs were evaluated by cytotoxic T lymphocyte assay. Following immunisation, mice were challenged by subcutaneous injection on their abdomen with tumour cells expressing ovalbumin and investigated for inhibition of tumour growth. Furthermore, an IFN-É£ ELISpot assay was performed to enumerate the antigen-specific effector cells secreting IFN-É£. Results showed that constructs with C16 lipids at the N-terminus formed long β-sheet fibrils and induced higher CD8+ T cell proliferation and IFN-É£ secretion compared with constructs containing internal placement of lipids. Constructs with small nanoparticles or beta-sheet secondary structures showed high cytolytic activity and tumour growth inhibition (Figure 1). Future direction aim to investigate the impact of these particles on humoral immune response in vivo.

Biography:

Bita is currently a third year PhD student (started from 2012) at the University of Queensland in the field of chemistry and molecular biosciences. She got her Pharm D. from the Tehran University of medical sciences and has got international working experience with 3 years of work in Japan as a visiting scholar in Kobe Gakuin University and working collaboration with Nisshin Kasei a pharmaceutical company.

Abstract:

O-glycosides, found on the cell wall of fungi, viruses and bacteria, are commonly attached through the hydroxyl group of serine and threonine. Mannose receptor, a front-line receptor in the human immune system, is known to bind bacterial, fungal and viral glycosides.1, 2 Subsequently, synthesis of mannosylated subunit vaccines could allow for new targets in the activation of the immune system in a safer and more effective approach.2 This study focuses on the complex synthesis and analysis of a library of O-mannosylated lipo-peptides designed to investigate mannose receptor binding properties for potential use in vaccine design and targeting. Here, a library of fluorescently-labelled dendrimers containing one or more mannosylated moieties (separated by a variable-length spacer) and the ovalbumin CD4 antigen [OVA(323-339)] was synthesised using solid phase peptide synthesis on Rink Amide resin (Figure 1-A). Figure 1 (A) Compound library containing OVA(323-339) antigen, lipoaminoacids (Laa), mannose and a fluorescent tag (FAM). (B) CD4+ T cell proliferation post 3rd immunisation for mannosylated vaccine constructs (G1-3) and controls (G4-8) indicating T cell activation related to structural properties. Results: Fluorescent glycol conjugate and dendritic cell targeting lipo-peptides have been successfully synthesised using Fmoc solid phase peptide synthesis and click chemistry techniques and purified using RP-HPLC. Compounds were analysed for purity and size using TEM. Uptake studies, performed on F4/80+ and CD11c+ cells, showed significant uptake for all glycosylated lipo-peptides when compared to the un-glycosylated controls. Furthermore, a mannan inhibition study confirmed receptor-mediated uptake. Synthetic strategies, characterisation, and preliminary in vitro uptake studies will be presented. Conclusion: We were able to successfully synthesise, purify and characterise fluorescently-labelled glyconjugate and dendritic cell targeting lipo-peptides in milligram quantities. In vitro analysis reinforces the use of glycoconjugates as targeting moieties towards APCs for applications in enhanced vaccine and drug delivery. Mannosylated vaccine constructs were shown to successfully increase endogenous CD4+ T cells (Figure 1-B) the constructs were able to activate T helpers depending on their structural properties. Results from in vivo studies including cytokine analysis, antibody response, and T cell proliferation will be discussed and presented.

Biography:

Khairunnisa graduated with a Diploma in Pharmaceutical Sciences and Technology from Temasek Polytechnic, Singapore in 2010. Upon graduating, she obtained a Bachelor of Science (Biochemistry) with Honours Class I from the University of Queensland, Australia in 2012. She is currently holding a University of Queensland International Scholarship for her postgraduate studies. During her studies, she has received various travel awards to attend workshops and conferences abroad. Currently, she is finilizing her PhD under the supervision of Prof. Istvan Toth and Dr. Mariusz Skwarczynski at the University of Queensland.

Abstract:

For the past decade, Group A Streptoccocus (GAS) has been one of the top ten pathogens causing mortality and morbidity. Treatment with antibiotics has proven to be successful; however,c the lack of early medical attention could lead to invasive GAS infection. In addition, rheumatic heart disease, dubbed as the ‘silent killer’, is the most critical sequelae of GAS, claiming more than 1 million lives each year.1 Our vaccine strategy utilizes the lipid core peptide (LCP) as a self-adjuvanting system2 in conjunction with liposomes as a delivery system. Liposomes are known for their efficacy in delivering antigens as well as for their targeting capability.3,4 Two epitopes were used, a) J14, KQAEDKVKASREAKKQVEKALEQLEDKVK, derived from the surface associated M protein of GAS; b) P25, KLIPNASLIENCTKAEL, a universal T-helper epitope. Seven different peptides (branched and linear), were synthesized using standard solid phase peptide synthesis and purified (≥95%) to attain moderate to high yields (44-80%). Liposomes were formulated giving an average size of 170 nm and a zeta potential of +57 mV. All compounds had varying percentages of encapsulation efficacy ≥65%. The lead vaccine candidate (liposomes encapsulating P25-K(J14)-LCP) had the highest encapsulation efficacy of 98%. Mice immunized intranasally with the lead vaccine candidate elicited the highest IgG and IgA antibody titres against J14 compared to all vaccine candidates and positive controls which included known adjuvant, cholera toxin B subunit. In addition, mice also retained high levels of serum IgG five months post final immunization. In conclusion, we prepared the first LCP-nanoliposome-based peptide vaccine candidate against GAS.

Biography:

Mala Menon, PhD in Pharmaceutics from Mumbai University, is currently Professor of Pharmaceutics at the Bombay College of Pharmacy, Mumbai, INDIA. Experience- Industry- 2 yrs; Teaching – 30 years. Key research areas - Drug Delivery Systems-Conventional & Novel type, Pulmonary & Nasal Delivery Systems, Novel Vaccine Delivery Approaches, especially mucosal vaccines, Probiotic formulations, Novel Veterinary formulations. Research projects- Government & Industry sponsored- around 25; Publications- National & International-34; Presentations- more than 80; Book chapters- 2; Patent applications filed- 4.

Abstract:

Vaccines given by the mucosal routes like nasal, pulmonary, buccal and oral can prove to be an effective alternative to conventional parenteral vaccines, since majority of human pathogens enter the body via mucosal surfaces. However, delivery of antigens through mucosal route is difficult, as these antigens have to be taken up by M-cells to induce an immune response. Multiparticulate systems like liposomes, nanoparticles (NP) which are easily taken up by M cells, can be explored as carriers for mucosal delivery of these antigens. Klebsiella pneumonia (KP) is one of the commonest causes of nosocomial infections in human beings, which are often difficult to treat due to the antibiotic resistance developed. In the present study, NP – based systems of KP capsular polysaccharide (KP-CPS) for mucosal immunization by nasal and oral inhalation delivery were prepared and evaluated for their immunogenicity. Capsular polysaccharide (KP-CPS), the antigenic fraction was extracted from K. pneumoniae by hot phenol extraction method. Chitosan NP co-entrapping KP-CPS and DLmT were prepared by ionotropic gelation method. Further, NP were spray dried with lactose as carrier to obtain inhalable (DPI) formulation. In vivo efficacy studies of developed systems were carried out in female Wistar rats via mucosal routes (intranasal and pulmonary), and antibody titres were measured by ELISA (IgG and IgA), followed by serum bactericidal assay. Nanoparticles with particle size around 470 nm and entrapment efficiency of 87.9% for KP-CPS were obtained. The spray dried formulation were obtained as spherical particles (average particle size 3.6 ± 1.2 micron, MMAD 2.66 μm and GSD of 2.71 μm). Results of antibody (IgG & IgA) titres as well as the serum bactericidal assays have revealed superior protective effect conferred by mucosal vaccine compared to the injectable vaccine.

Biography:

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.

Abstract:

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.

Biography:

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.

Abstract:

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".

Biography:

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.

Abstract:

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.

Biography:

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’.

Abstract:

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.

Biography:

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.

Abstract:

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.

Biography:

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.

Abstract:

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.

Biography:

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.

Abstract:

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.

Biography:

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.

Abstract:

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”.

Biography:

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.

Abstract:

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 [1] and IM injection with a 1/100th of the vaccine dose in mice [2]. 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.

Biography:

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.

Abstract:

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.

Biography:

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.

Abstract:

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.