Injecting Drug Users: Social Networks And Molecular Epidemiology Of The Hepatitis C Virus
Funder
National Health and Medical Research Council
Funding Amount
$543,868.00
Summary
The hepatitis C virus (HCV) continues to spread among injecting drug users (IDUs) in Australia at a very high rate, despite success in preventing the spread of HIV in the same groups; the complete reasons for this remain unclear. There is an urgent need for the HCV epidemic among IDUs to be contained. To do so, we must better understand the ways in which it is spreading among IDUs. Much is known about risk behaviours of individual IDUs and how they contribute to HCV transmission; much less is kn ....The hepatitis C virus (HCV) continues to spread among injecting drug users (IDUs) in Australia at a very high rate, despite success in preventing the spread of HIV in the same groups; the complete reasons for this remain unclear. There is an urgent need for the HCV epidemic among IDUs to be contained. To do so, we must better understand the ways in which it is spreading among IDUs. Much is known about risk behaviours of individual IDUs and how they contribute to HCV transmission; much less is known about how these behaviours are modified by the influence of the IDUs peer group, especially their immediate and intimate social networks. Despite its importance in influencing attitudes and behaviours, and therefore HCV transmission, this has never been studied in Australia, nor, in relation to HCV, in the world. We hope that by studying social and risk networks of IDUs we shall discover new ways in which control of the HCV epidemic can be achieved in Australia. We intend to do this among two groups of young IDUs, one of Vietnamese ethnicity, located in the one suburb of Melbourne. By using field techniques for gathering information (ethnography), and sophisticated analytic techniques to understand how these networks are formed and influence behaviours, we hope to be able to identify interventions which work at the level of the social group rather than the individual in bringing about the behaviour change necessary to prevent HCV transmission. To ensure that the risk networks we describe are as influential as they appear, and to discover more about the variability of HCV, we will also be investigating the relationship between the various strains of HCV in members of the IDU networks, particularly as another measure of the connectedness of networks and network members. This will be done using sophisticated genetic analysis of the HCV obtained from network members by blood test.Read moreRead less
Roles Of Enzymes Of The Dipeptidyl Peptidase Gene Family In Human Liver
Funder
National Health and Medical Research Council
Funding Amount
$79,750.00
Summary
Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infe ....Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infections will progress to liver failure or liver cancer within 30 years. Diabetes afflicts 150 million people, and 90% have Type 2 diabetes. We request funding of our research on a family of enzymes highly prospective as targets for novel therapies for these diseases. We are internationally recognised experts on this enzyme family and on liver disease. The prototype member of this enzyme family, dipeptidyl peptidase (DP) IV, is being targeted by novel drugs that are in phase III clinical trials for Type 2 diabetes. Family member fibroblast activation protein (FAP) is targeted by novel anti-cancer drugs We were first to clone and lodge patent applications for two new enzymes of this family, DP8 and DP9. Our research proposal would lead to determination of whether FAP, DP8 and-or DP9 are valuable targets for novel liver disease therapeutics and facilitate generating the development of such therapeutics by a more thorough understanding of the activities and roles of these enzymes Completion of this project will greatly increase our understanding of these enzymes and their roles in chronic liver injury. This work can potentially lead to the development of specific inhibitors of enzyme function designed to relieve liver damage.Read moreRead less
Pandemic Influenza Vaccine: Exploiting The Conserved HA Cleavage Site
Funder
National Health and Medical Research Council
Funding Amount
$243,300.00
Summary
Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preve ....Influenza virus needs to cleave its surface spike protein, hemagglutinin or HA, to become mature and infectious. This project is aimed at producing a vaccine that will block the cleavage thus rendering the virus non-infectious. To achieve this, we will use synthetic fragments (called peptides) of the viral HA spike protein mimicking its cleavage site to immunize mice. This will produce specific antibodies that will bind to the cleavage site while the virus is inside the infected cell, thus preventing the viral spike protein from being cleaved and remain immature. This idea is particularly suited to fight the bird flu, as all pathogenic bird influenza viruses cleave HA spike proteins within the infected cell.Read moreRead less
Simplified Process Methods For Mass Vaccine Manufacture
Funder
National Health and Medical Research Council
Funding Amount
$158,393.00
Summary
The ideal way to protect against pandemic bird flu is to vaccinate all Australians as soon as possible after a dangerous strain starts to spread. Current manufacturing technology, which begins by making an infectious virus in chicken eggs, is unable to quickly deliver a mass vaccine to the entire Australian population. The existing process is slow, meaning that it will take several months before enough vaccine is available even to protect personnel working in essential services. The product from ....The ideal way to protect against pandemic bird flu is to vaccinate all Australians as soon as possible after a dangerous strain starts to spread. Current manufacturing technology, which begins by making an infectious virus in chicken eggs, is unable to quickly deliver a mass vaccine to the entire Australian population. The existing process is slow, meaning that it will take several months before enough vaccine is available even to protect personnel working in essential services. The product from chicken eggs is rendered safe after manufacture by breaking the virus structure. This make then break strategy reduces vaccine effectiveness meaning that even fewer individuals can be effectively protected per vaccine batch. Recent scientific progress has demonstrated that it is possible to make a non-infectious empty virus shell (a so-called virus-like particle) inside cells. This new product is able to provide full protection against a lethal influenza challenge, when administered nasally. However, these particles are very difficult to purify from contaminants that are packaged into the particles during manufacture in cells. These contaminants can cause an adverse reaction when the product is given to humans, meaning that although the product is effective it remains difficult to mass produce. A manufacturing problem remains. To overcome this manufacturing problem we will seek to assemble vaccine particles in vitro, building the particle from purified protein. Existing technology for manufacturing pure pharmaceutical protein is well-established and safe, and allows mass manufacture of contaminant-free product. This new make don't break manufacturing strategy is similar to that chosen by Merck to deliver a safe and effective vaccine, for cervical cancer, to mass market. Our key aim is to adapt this efficient manufacturing strategy to the manufacture of influenza vaccine. If successful, we will be able to immunize the Australian population using existing national biomanufacturing capability, within weeks of new strain identification, and without the requirement for high-level containment during manufacture.Read moreRead less
Rapid Point Of Care Detection Of Avian Influenza Virus Using Ion-Channel Switch Biosensor
Funder
National Health and Medical Research Council
Funding Amount
$425,400.00
Summary
The project aims to demonstrate a rapid, Point-of-Care test based on the Ion Channel Switch (ICS_) Biosensor for the detection and identification of Avian Influenza (AI) Virus in respiratory specimens. This proposal combines the extensive scientific skills and experience of the Institute of Medical and Veterinary Science (IMVS), Adelaide with the experience and existing capability of Ambri Ltd, Chatswood Sydney, to adapt an existing ICS_ Biosensor for the detection of avian influenza virus in cl ....The project aims to demonstrate a rapid, Point-of-Care test based on the Ion Channel Switch (ICS_) Biosensor for the detection and identification of Avian Influenza (AI) Virus in respiratory specimens. This proposal combines the extensive scientific skills and experience of the Institute of Medical and Veterinary Science (IMVS), Adelaide with the experience and existing capability of Ambri Ltd, Chatswood Sydney, to adapt an existing ICS_ Biosensor for the detection of avian influenza virus in clinical specimens. The existing ICS_ Biosensor has been shown to have reactivity with inactivated Influenza A (H1N1 and H3N2 _ current, circulating human strains) and with recombinant Nucleoprotein. This unique mix of experience and infrastructure will permit the demonstration a rapid, point-of-care test for Avian Flu within the tight six months schedule.Read moreRead less
Are Routine Healthcare Worker Hand Hygiene Protocols (soap/water, Alcohol-based Handrub) Effective Against Influenza?
Funder
National Health and Medical Research Council
Funding Amount
$99,950.00
Summary
Although influenza is mainly spread from person-to-person by aerosol transmission (coughing, sneezing etc), there is growing evidence that spread also occurs on the hands of infected patients and their carers (non-aerosol transmission). Because of this, health authorities now recommend the use of careful hand hygiene (HH: hand washing with soap-water or use of alcohol-based hand rub solutions [ABHRS]) by healthcare workers (HCWs) and patients. However, despite these recommendations, there are no ....Although influenza is mainly spread from person-to-person by aerosol transmission (coughing, sneezing etc), there is growing evidence that spread also occurs on the hands of infected patients and their carers (non-aerosol transmission). Because of this, health authorities now recommend the use of careful hand hygiene (HH: hand washing with soap-water or use of alcohol-based hand rub solutions [ABHRS]) by healthcare workers (HCWs) and patients. However, despite these recommendations, there are no data that demonstrate the effectiveness of such HH protocols. This project aims to assess the clinical effectiveness of four HH protocols (handwashing with soap-water, alcohol-only ABHRS, two alcohol-chlorhexidine ABHRS) in common use in Australian hospitals to see which protocol is best for killing influenza virus. We also plan to assess how long influenza virus remains infectious on HCWs hands if they fail to use appropriate HH. Since it could be dangerous to use live avian influenza virus in this study, we plan to use the H1N1 influenza A strain that was a component of the influenza vaccine administered to most HCWs in 2005. Thus, only HCWs with protective immunity to H1N1 will participate in a series of tests in which they will have their hands artificially contaminated with a known concentration of live H1N1 before using either no HH, or one of the four HH protocols, followed by an assessment (virus culture and molecular tests) or the amount of H1N1 surviving on their hands after each protocol. Some selected HCWs will also have the amount of surviving virus assessed 30 and 60 minutes after contamination to identify how long H1N1 survives on HCWs hands should they not use appropriate HH. Following all protocols, all HCWs will perform a detailed surgical scrub (similar to surgeons before an operation) to make certain that all H1N1 is killed to avoid any infection of themselves or their contacts. The study will be undertaken in special, secure, negative-pressure rooms at Austin Hospital away from patient care areas to provide maximum safety conditions. All virus culture and molecular tests will be performed in the virus Identification Laboratory at the Victorian Infectious Disease Reference Laboratory (VIDRL), Melbourne. Results of the study should help identify which HH protocol provides the most protection against influenza.Read moreRead less
Safety Of Hendra Virus Anti-G Glycoprotein Monoclonal Antibody In Humans
Funder
National Health and Medical Research Council
Funding Amount
$400,000.00
Summary
Hendra virus infection in humans is a serious, and often fatal, disease. No cure exists for Hendra infection and existing treatments are ineffective. Recently, a human monoclonal antibody has shown great promise in protecting animals from developing the disease. This project aims to perform preclinical safety testing and a Phase I clinical trial to establish the safety profile of this antibody such that it can be used to prevent Hendra infection in humans exposed to the disease.
Chimeric Virus-like Particles (VLPs) Displaying H1, H3 And H5 Haemagglutinins - Construction And Immunogenicity
Funder
National Health and Medical Research Council
Funding Amount
$207,543.00
Summary
Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can b ....Virus-like particles (VLPs) provoke strong immune responses in the body. We have developed a novel VLP system that allows the production of VLPs containing foreign vaccine antigens of much larger size than previously possible, and have shown that these VLPs provoke strong immune responses in mice without the use of adjuvants. The capacity of these VLPs is large enough to accommodate the most important vaccine antigen of influenza, the haemagglutinin (HA) molecule. We will test whether VLPs can be produced containing each of the three most important HA types _ H1 and H3 that are currently circulating in man, and H5 (avian) that is considered a pandemic threat. VLPs will be tested for their ability to induce neutralizing antibody and cellular immune responses in mice, and for their ability to protect ferrets from influenza infection. If successful, the HA-VLP system would provide a method for the rapid production of new influenza vaccines using large-scale fermentation technology as for hepatitis B and many other vaccines, rather than eggs or cell culture as used for current influenza vaccines.Read moreRead less