Combination Antiviral And Immune Therapies For Hepatitis B Virus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Hepatitis B virus (HBV) causes acute and persistent (chronic) infection with varying degrees of liver damage and a strong association with the development of liver cancer. Worldwide ~ 250 million people have persistent HBV infection and while a HBV vaccine is available that protects against infection, current treatments for existing infection are largely ineffective. We wish to study a combination of antiviral drug therapy and vaccination with DNA vaccines, to develop new treatment protocols for ....Hepatitis B virus (HBV) causes acute and persistent (chronic) infection with varying degrees of liver damage and a strong association with the development of liver cancer. Worldwide ~ 250 million people have persistent HBV infection and while a HBV vaccine is available that protects against infection, current treatments for existing infection are largely ineffective. We wish to study a combination of antiviral drug therapy and vaccination with DNA vaccines, to develop new treatment protocols for persistent hepatitis B virus (HBV) infection. The human HBV is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Therapies will be tested in ducks infected with the duck hepatitis B virus (DHBV) as these animals provide the only model system available in Australia for development of HBV therapies. DHBV-infected ducks will be treated with a new and extremely potent antiviral drug Entacavir (ETV; Bristol-Myers Squibb). Drug treatment will be combined with various DNA vaccination protocols, including new strategies that involve DNA vaccine priming and recombinant fowlpoxvirus (rFPV) boosting of immune responses. Inoculation of DNA vaccines and rFPV results in expression of viral proteins that are presented to the immune system and evoke strong immune responses. 'Prime boost' protocols with DNA vaccines and rFPV have shown promise for protection against and treatment of human immunodeficiency virus (AIDS virus) infection. We will assess the effect of treatment by measuring levels of DHBV in liver and blood, clearance of infected cells and serological changes. The ultimate aim is to develop successful therapies that can then be applied to treatment and elimination of HBV infection in humans.Read moreRead less
Development Of Improved Vaccine Strategies For Measles Using Plant-derived Edible Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$331,980.00
Summary
Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the cur ....Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the current vaccination strategy are: a) doesn't work in children less than 1 year of age, b) must be kept cold c) must be given by injection. We believe that a plant derived edible vaccine for measles will address the limitations of currently available vaccine i.e. we can give it children under the age of 1 year, it can be eaten and doesn't have to be kept cold.Read moreRead less
Enhancement Of Mucosal Immunity And CTL Avidity Against HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$553,070.00
Summary
Production of strong antiviral immunity at the local mucosa (genito-rectal track) is essential for protection against HIV-AIDS. We believe that expression of small hormone-like molecules known as Th2 cytokines IL-4-IL-13 negatively influence the generation of protective immunity against HIV. Thus we aim to counteract these effects by co-expressing proteins known as chemokines together with vaccine antigens to improve the quality of mucosal vaccine immunity.
Immune Therapies For Chronic Hepatitis B Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$359,085.00
Summary
Hepatitis B virus (HBV) causes acute and chronic infection leading to severe liver damage in many patients and increased risk of primary liver cancer. Worldwide ~350 million people have chronic HBV infection and, while a HBV vaccine is available that protects against new infections, current antiviral drug treatments for existing infection are largely ineffective. Thus, the aim of our project is to develop new treatments for chronic HBV infection using vaccination approaches. These therapies will ....Hepatitis B virus (HBV) causes acute and chronic infection leading to severe liver damage in many patients and increased risk of primary liver cancer. Worldwide ~350 million people have chronic HBV infection and, while a HBV vaccine is available that protects against new infections, current antiviral drug treatments for existing infection are largely ineffective. Thus, the aim of our project is to develop new treatments for chronic HBV infection using vaccination approaches. These therapies will be tested in ducks infected with the duck hepatitis B virus (DHBV), a model for human HBV infection. In brief, DHBV-infected ducks will be treated with a new antiviral drug, Entecavir (ETV) developed by Bristol-Myers Squibb, which blocks virus replication. To accelerate clearance of infected cells before drug-resistant viruses can emerge, the ducks will also be treated in combination with different novel therapeutic vaccines designed to induce strong humoral and cell mediated immune responses. Based on outcomes in initial experiments, we will adjust the vaccination protocol in ETV-treated ducks to maximize reductions in the levels of DHBV in liver and bloodstream, rates of death and clearance of DHBV-infected hepatocytes. Our ultimate goal is to define a protocol for combination antiviral and vaccination treatments that allows elimination of HBV infection, or that achieves a level of control of infection that eliminates ongoing disease by reducing virus loads to virtually undetectable levels.Read moreRead less
Understanding The Variation In Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$417,750.00
Summary
Frontotemporal dementia (FTD) is one of the non-Alzheimer dementias which accounts for between 12 and 20% of all dementia and as much as 50% of early onset dementia. It is characterised by marked behavioural change and thus patients with this disease present a major management challenge. The cause of FTD is unknown and at present there is no effective treatment for the disease. There are a number of different clinical subtypes of FTD, namely behavioural variant, language variant, and FTD with mo ....Frontotemporal dementia (FTD) is one of the non-Alzheimer dementias which accounts for between 12 and 20% of all dementia and as much as 50% of early onset dementia. It is characterised by marked behavioural change and thus patients with this disease present a major management challenge. The cause of FTD is unknown and at present there is no effective treatment for the disease. There are a number of different clinical subtypes of FTD, namely behavioural variant, language variant, and FTD with motor neuron disease (FTD+MND). Similarly there are pathological subtypes of FTD (Pick's disease, frontotemporal lobar degeneration and FTD with ubiquitin-positive MND inclusions). However, there appears to be little correspondence between these two subdivisions. The purpose of this study is to investigate the pathological differences and similarities between the different clinical subtypes of FTD. Furthermore, we will investigate the changes in brain atrophy which occur over the course of the disease to allow us to understand better the initial focus of the disease. We will also evaluate the role of cellular protein changes (ubiquitin and tau) in the pathogenesis of neuronal death. This research will allow us (i) to better diagnose and characterise FTD and (ii) establish any common mechanisms of neurodegeneration in the subtypes of FTD.Read moreRead less
Securing Web-based Services by Policy Coherence and Proof-checking. This project aims to develop a provably correct cybersecurity system for workflows, which enables organizations to provide flexible and more secure web-based services and business communication. The project expects to generate new knowledge, theoretic advancement and result in new technologies in the areas of internet of things and cybersecurity. The expected outcomes include a software tool with documentation, which helps organ ....Securing Web-based Services by Policy Coherence and Proof-checking. This project aims to develop a provably correct cybersecurity system for workflows, which enables organizations to provide flexible and more secure web-based services and business communication. The project expects to generate new knowledge, theoretic advancement and result in new technologies in the areas of internet of things and cybersecurity. The expected outcomes include a software tool with documentation, which helps organisations achieve operational excellence and security, and maintain a trusted environment for end users. This system will provide significant economic and commercial benefits to business and end users with highly secured web-services and improved productivity through a coherent framework and proof-checked workflows.Read moreRead less
Internet Timing for the Ages: Establishing the New Timekeeping System. All computers incorporate a software clock, essential to myriad software applications. An economic way to synchronize such clocks is over a network, however the approach the Internet currently depends upon is unreliable and vulnerable. This project aims to establish a new architecture for networked timekeeping, built on future-proofed fundamentals, that will for the first time address each of accuracy, reliability, and trust. ....Internet Timing for the Ages: Establishing the New Timekeeping System. All computers incorporate a software clock, essential to myriad software applications. An economic way to synchronize such clocks is over a network, however the approach the Internet currently depends upon is unreliable and vulnerable. This project aims to establish a new architecture for networked timekeeping, built on future-proofed fundamentals, that will for the first time address each of accuracy, reliability, and trust. The expected outcome is a national prototype, serving the public with accurate and trusted time, that will form the basis of the next generation timekeeping system for the Internet and the Internet of Things. Expected benefits include enhanced productivity across the digital economy, and resilience to GPS failures.Read moreRead less