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
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.
A New Non-invasive Diagnostic Technique Based On Detection Of Exhaled Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$179,300.00
Summary
We developed a special collection mask and showed that the breath of people with colds or flu contains a tiny amount of virus. Currently, diagnostic samples are collected by putting a tube into the airways - this is very uncomfortable. Our masks may provide a new and more comfortable way to diagnose lung infections. We want to build better masks and ways to detect viruses and bacteria to test out this method. This may create a new test that will improve diagnosis and treatment.
Assessment Of Bilateral Oedema By Bioelectrical Impedance Analysis
Funder
National Health and Medical Research Council
Funding Amount
$180,000.00
Summary
Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estima ....Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estimated that at any time 100000 women are suffering from post- mastectomy lymphedema in Australia alone. Treatment of breast cancer alone therefore, given the incidence of the disease, produces a large at-risk population. Add to this other causes of oedema and the magnitude of the problem becomes clearly apparent. The presence of chronic oedema is often a disfiguring and disabling disorder, usually accompanied by pain, recurrent infection, reduced mobility and impaired function. In acute oedema the problem often resolves with recovery from the underlying pathology. In chronic oedema, progression may be arrested by early intervention including complex physical therapy (exercise regimen, compression bandaging, and massage) which is effective in reducing limb volume, in improving the quality of life, function and body image of patients. Although the assessment of oedema is clearly of clinical importance, relatively few objective and accurate techniques for its measurement exist. Research conducted over the past decade by the applicants has pioneered the Use of Bioelectrical Impedance Analysis for the assessment of lymphedema. This study aims to translate this basic research into clinical practice. Sensitivity and specificity studies will establish normative and threshold values for impedance measurements that can be used as presumptive indicators of oedema. User friendly technology and equipment suitable for clinical use will be developed which should improve treatment therapies.Read moreRead less
We will conduct a clinical trial of the effectiveness of a continuous auditory display of an anesthetized patient's respiratory status. Expired carbon dioxide monitoring has helped reduce respiratory incidents since its widespread introduction in the late 1980s, but a continuous auditory display of respiratory status may reduce incidents further. We will conduct a clinical trial with 10 anaesthetists of continuous auditory respiratory monitoring. Successful outcome may lead to commercial uptake.
Development And Clinical Evaluation Of A Depth Of Anaesthesia Monitor
Funder
National Health and Medical Research Council
Funding Amount
$424,785.00
Summary
Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a g ....Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a general anaesthetic each year, about 2000 will suffer an episode of awareness. More than 60 million people around the world have an anaesthetic, and so the problem is substantial. This suggests the potential benefits (health outcomes, commercial gains) are very great. In 2000 less than 5% of US hospitals used BIS monitoring; the current figure in the US is about 69% of the best-rated hospitals (US News and World Report) and 78% of teaching hospitals. A similar rapid growth is occurring in Australia and Europe. We are working with a successful Australian Company (Compumedics Ltd) to develop a better awareness monitor. We plan studies in groups of patients have surgery.Read moreRead less
A Novel Treatment For Ameliorating Retinal Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$366,685.00
Summary
Retinal vascular disease is a leading cause of blindness and is currently treated by laser photocoagulation surgery. Although successful, this treatment is associated with serious side effects. Recently, Ellex Pty has developed a novel laser called the 2RT laser that is likely to be effective without the accompanying side effects. This study will allow examine the effect of the 2RT laser in animal models of retinal vascular disease so as to complete preclinical development of this laser.
Development Of A Smart Arthroscopy System And Prototype Probe For Joint Tissues
Funder
National Health and Medical Research Council
Funding Amount
$230,632.00
Summary
This project relates to the ever growing use of arthroscopy in the management of joint defects. An innovative probe that will combine all the molecular, microstructural and biomechanical characteristics of joint articular cartialge and bone for the purposes of diagnosis, treatment, treatment-related decisions, comparison of the effectiveness of treament methods and post treatment evaluation will be developed. This system will produce spin-offs for artrhoscopy of other soft tissues and bodies.
Development And Evaluation Of Novel Anti-inflammatory Products Derived From An Indigenous Medicinal Plant
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
This collaborative project between researchers at the University of South Australia and Indigenous traditional owners from Northern Kaanju homelands (Cape York Peninsula, Qld) will develop and evaluate products derived from the Northern Kaanju medicinal plant Dodonaea polyandra. Extracts of the plant and novel compounds isolated from it have anti-inflammatory activity. These have the potential to be used in inflammatory diseases such as dermatitis, arthritis and inflammatory bowel disease.