Development Of Chimeric Hepatitis B Virus Like Particles As A Vaccine Delivery Platform For Multiple HIV-1 Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$139,500.00
Summary
The small envelope protein of hepatitis B virus (HBsAg) can self-assemble into highly organised viruslike particles with about 150 HBsAg-proteins forming a virus-like particle (VLP). VLPs induce an effective immune response, mainly against the exposed major antigenic site, the hydrophilic ‘a’- determinant region. To create a novel HBsAg-specific vaccine vector, foreign epitopes were inserted into the major antigenic site allowing surface orientation of the inserted sequence. Pilot studies involv ....The small envelope protein of hepatitis B virus (HBsAg) can self-assemble into highly organised viruslike particles with about 150 HBsAg-proteins forming a virus-like particle (VLP). VLPs induce an effective immune response, mainly against the exposed major antigenic site, the hydrophilic ‘a’- determinant region. To create a novel HBsAg-specific vaccine vector, foreign epitopes were inserted into the major antigenic site allowing surface orientation of the inserted sequence. Pilot studies involving the vaccination of mice with VLPs containing an epitope derived from the AIDS-virus (human immunodeficiency virus 1, HIV-1) or various hepatitis C virus-specific epitopes resulted in high titre antibody responses. This project aims for the development of a multi-component vaccine targeting a non-structural HIV-1 protein and therefore, avoiding the selective pressure directed against the structural proteins. The non-structural HIV-1 tat-protein is a multi-functional protein with an extracellular mode to sensitise uninfected cells for HIV-1 infection and to reactivate HIV-1 from quiescently infected cells. The use of eight tat-sequences is sufficient to provide coverage against 99% of HIV-1 sequences. We will develop hybrid particles that are composed of different sets of chimeric HBsAg proteins each containing a distinct tat-epitope. With this application, we aim to develop hybrid particles for the delivery of the complete set of tat-epitopes. The hybrid particles will be used for vaccination studies in mice, and the antibodies assessed by an in-vitro assay. This will lead to the development of a therapeutic and-or prophylactic HIV-1 vaccine, which could be used either for mass immunisation or in support of combination drug therapy and would have all the cost and production advantages of the widely used hepatitis B vaccine.Read moreRead less
External Therapeutic Device To Support Rehabilitation Of The Hand Following Trauma Or Surgery
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and ....The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and tendon sheath adhesions or non-functional scar tissue formation, continuous passive motion (CPM) is often indicated. Additionally, for people with reduced mobility of the hand due to upper limb paralysis, such as those with cervical spinal cord injury, stroke, cerebral palsy or peripheral nerve injury, disregard for management of the maintenance of the joint range of motion of the effected hand will result in contracture and limited joint range of motion. Such syndromes will reduce hand function, which is already limited by paralysis, and will negatively affect potential outcomes for aggressive rehabilitation techniques, such as tendon transfer surgery and functional neuromuscular stimulation. Therefore, in such cases, CPM is also indicated. Current devices applying CPM have shown to be effective in minimising the syndromes indicated above and these results are summarised in the Background and Research Plan attached to this proposal. Unfortunately, the use of such devices is not always prescribed by clinicians. This is due, mainly, to the limitations of these devices that are in the marketplace. These limitations include lack of secure finger placement, lack of portability, the inability to provide specialised therapy to specific joints and inflexible programming. This proposal introduces an improved device to be developed and these improvements form the proposal aims below. Given such an improved device, which can overcome many of the problems with current CPM machines, it is likely that that the clinical application of CPM will achieve the greater degree of prescription and application in hand rehabilitation. These improvements should overcome the clinical reticence to use these devices and restore a balance by increasing their use to the level that the scientific literature indicates they should have. The overall aim of the proposal is to take the device to a stage where it is ready for clinical trial.Read moreRead less
Modulating Immune Responses By Targeting Dendritic Cells Using Dendritic Cell Specific Markers.
Funder
National Health and Medical Research Council
Funding Amount
$197,750.00
Summary
The ability to modulate immune responses would have major health benefits. Dendritic cells (DC) are key regulators of the immune system. Different types of DC possess different cell surface molecules and have differing regulatory functions. We have identified four novel DC surface molecules that can be used to target different types of DC. We aim to use antibodies against these molecules to either enhance the effectiveness of vaccines or to suppress autoimmune diseases.
Seminal Plasma Cytokines As Novel Fertility Diagnostics In Men
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men ha ....Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Current IVF therapy is not successful when the underlying reason for infertility is failure of the maternal tissues to support embryo implantation. We have discovered signaling proteins present in male semen that act in the female reproductive tissues to prepare for embryo implantation and healthy pregnancy. Recently we have identified those proteins and have shown that some men have an imbalance in seminal proteins that leads to immune rejection of the embryo in the female partner. This project aims to develop a new test for male fertility that is based on seminal plasma proteins and independent of existing sperm count tests. Furthermore we will determine whether seminal protein imbalance can result from the �silent� presence of male reproductive tract infection.Read moreRead less
Commercialisation Of A Glycoprofiling Diagnostic Kit And Novel Therapies For Biofilm Related Respiratory Disorders
Funder
National Health and Medical Research Council
Funding Amount
$203,050.00
Summary
Our preliminary studies have shown that a group of patients who suffer from chronic inflammatory disease and have bacterial biofilm identified on their mucosa have worse outcomes even after surgery. We have shown that they lack certain small protein and sugar molecules on their respiratory lining. We aim to use this technology as a diagnostic tool to aid the doctor in prescribing the appropriate treatment for these patients to prevent bacteria regrowing in their respiratory tract.
Ultrasonic Blood Pressure Measurement On Implanted Biomedical Surfaces
Funder
National Health and Medical Research Council
Funding Amount
$170,250.00
Summary
The project would develop a prototype device reporting blood pressure on a biomedical implant surface. The device would extract data in real time from a standard ultrasound scanner that images the implant. The School of Mathematical Sciences at Monash University will be contracted to develop this ultrasound pressure sensor.
A Novel Device To Improve Renal Blood Flow In Cardiorenal Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$198,900.00
Summary
The aim of this project is to assist in the development of a novel device to treat poor delivery of blood to the kidneys in conditions such as heart muscle weakness (chronic heart failure, CHF). Specifically we aim to build a prototype and test the device in a relevant animal model of CHF. Chronic heart failure is a major public health problem affecting >10% of the adult population over the age of 60 years. It is associated with high morbidity, mortality, frequent hospitalisation and major co ....The aim of this project is to assist in the development of a novel device to treat poor delivery of blood to the kidneys in conditions such as heart muscle weakness (chronic heart failure, CHF). Specifically we aim to build a prototype and test the device in a relevant animal model of CHF. Chronic heart failure is a major public health problem affecting >10% of the adult population over the age of 60 years. It is associated with high morbidity, mortality, frequent hospitalisation and major cost burden on the public health system. Weak heart muscle results in poor delivery of blood to the kidneys. Poor delivery to the kidneys activates circulating hormones which in turn further impair cardiac function by adverse effects on the heart. We have developed and patented a novel catheter based system for improvement of renal function via a purpose built device. Proof-of-concept studies have shown that the device should improve kidney blood flow in the setting of CHF. Given the huge public health problem of heart failure and the importance of the kidney in this setting, the commercial potential for a simple device that can be positioned via a catheter-based approach, permanently implanted is large. The device is currently being constructed by the Monash University Department of Engineering where expertise exists with regard to biomedical devices and materials engineering. A series of proof-of-concept studies will then be performed in sheep, as the vasculature of the sheep roughly approximates the dimensions of man. Sheep with CHF will have the device inserted percutaneously into the aorta. Measurements will be made of renal artery flow, relevant circulatory hormones and ultrasound of the heart at baseline (pre-deployment) and following deployment. We believe the above studies (should they be successful) will be sufficient to constitute definitive proof-of-concept and thus allow the device to be commercialised, most likely by a licensing arrangement with a device company.Read moreRead less
The Diagnosis, Biomarker Identification And Measurement Of Drug Efficacy In Mental Illness And Neurological Conditions.
Funder
National Health and Medical Research Council
Funding Amount
$119,050.00
Summary
Globally, 2 billion people suffer from a neuropsychiatric illness. The cost is more than US$2 trillion a year. Hampering early intervention is the current lack of definitive, quantitative techniques for diagnosis and measurement of treatment efficacy. This research will determine whether the disease fingerprints produced by a new technique, EVestG, are diagnostically unique (to schizophrenia, depression and Parkinson's disease) and sensitive to disease progression and treatment response.
Microfluidic Device Fo The Quantitative Assessment Of Blood Platelet Aggregation Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$270,114.00
Summary
This project will develop a low-cost microfluidic chip which utilises dynamic shear stress to assess the propensity of blood clotting. This tool will analyze a tiny sample of blood and will predict excessive or ineffective clotting. The project will develop the chip and a low-cost 'chip reader' such that the tool can be operated at the point of care with only basic training.