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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
Despite recent advances in therapeutic options, chronic viral infections, including infection with hepatitis C virus and hepatitis B virus, continue to be a significant cause of morbidity and mortality in Australia and affecting hundreds of millions of people worldwide. This R&D program aims to develop a cheaper drug formulation that is easier to deliver and more stable for transport to remote areas.
Monoclonal Antibodies Targeting Plasma Cells As Novel Therapeutic Agents And Diagnostic Tools
Funder
National Health and Medical Research Council
Funding Amount
$199,275.00
Summary
We have a new tool to identify a very rare immune cell type. This cell makes antibodies, powerful and exquisitely specific proteins that fight infection. In health, antibody-producing cells are beneficial, but in disease (rheumatoid arthritis, lupus and myeloma), these cells cause disease or death. Antibody-producing cells are long-lived. We have no means to specifically deplete them. We are developing reagents to identify and deplete antibody-producing cells to use as novel therapeutic agents.
New Technologies For Hierarchial Shotgun Sequencing Of Recalcitrant And Repetitive DNA
Funder
National Health and Medical Research Council
Funding Amount
$79,750.00
Summary
Many repetitive regions of genomes are difficult to sequence and to assemble. �Sequencing Aided by Mutation� (SAM) is a new sequencing technology, which overcomes many of the difficulties that hinder current sequencing methods. SAM involves forming randomly mutated copies of the target DNA. These copies can then be sequenced and new mathematical tools permit the original target sequence to be revealed from the mutant copies. Here the technology will be developed to aid sequencing of long repetit ....Many repetitive regions of genomes are difficult to sequence and to assemble. �Sequencing Aided by Mutation� (SAM) is a new sequencing technology, which overcomes many of the difficulties that hinder current sequencing methods. SAM involves forming randomly mutated copies of the target DNA. These copies can then be sequenced and new mathematical tools permit the original target sequence to be revealed from the mutant copies. Here the technology will be developed to aid sequencing of long repetitive DNA fragments in genomes.Read moreRead less
Rapid HIV-1 Tropism Testing Using Novel, Soluble Mimics Of The HIV-1 Coreceptors CCR5 And CXCR4
Funder
National Health and Medical Research Council
Funding Amount
$163,426.00
Summary
This proposal seeks to develop an inexpensive assay to determine whether HIV patients will benefit from treatment with new drugs referred to as CCR5 antagonists. These are effective against HIV strains that use the CCR5 coreceptor, therefore a patient�s HIV coreceptor usage must be assessed before commencing therapy. Current assays are complicated, slow and expensive. Using novel, soluble mimics of the coreceptors we will develop an ELISA based test that can be operated using standard equipment.
Production Of A Novel Humanised Anti Dendritic Cell Therapeutic Antibody For Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$202,500.00
Summary
A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be use ....A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be useful for the prevention of rejection in solid organ transplantation. If successful, it will selectively control graft versus host disease, without compromising the essential anti-viral immunity and desired anti-leukemia activity of the graft.Read moreRead less
NaviGAIT: New Software To Simplify Interpretation Of Gait Analysis Data
Funder
National Health and Medical Research Council
Funding Amount
$179,905.00
Summary
NaviGAIT is a new software package to support interpretation of gait analysis data. It is based upon Gait Profiling, a new technique to reduce the complexity of such data. At present data intepretation is restricted to a few expert clinicians. The new software will allow non-expert clinicians to interpret data and hence make gait analysis more accessible, cheaper and more clincally useful. A module of NaviGAIT specifically for children with cerebral palsy will be the first to be developed.
Phase 1 Clinical Trial Of Autologous Dendritic Cells To Induce Antigen-specific Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$165,125.00
Summary
We have previously generated modified dendritic cells in mice with the ability to suppress immune responses once they have started. This project will develop the dendritic cell vaccine as a platform technology for human clinical use. We aim to demonstrate, in a phase I clinical trial, the capacity of modified human autologous dendritic cells to suppress the immune response to a model antigen in a group of healthy volunteers and a group of patients with rheumatoid arthritis taking drugs for their ....We have previously generated modified dendritic cells in mice with the ability to suppress immune responses once they have started. This project will develop the dendritic cell vaccine as a platform technology for human clinical use. We aim to demonstrate, in a phase I clinical trial, the capacity of modified human autologous dendritic cells to suppress the immune response to a model antigen in a group of healthy volunteers and a group of patients with rheumatoid arthritis taking drugs for their diseaseRead moreRead less
Development Of Novel Anti-cancer And Immunosuppressive Drugs Derived From Pineapple Stems
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
We have discovered two molecules from pineapple stems that show anti-tumour activity in laboratory studies. One molecule, called ananain, blocks a cancer causing protein called Ras, which is defective in approximately 30% of all cancers. The other molecule, called canizain, stimulates the bodies own immune system to target and kill cancer cells. The proposed research seeks to provide proof of concept of the use of ananain and canizain as drug development targets. Once this early proof of princip ....We have discovered two molecules from pineapple stems that show anti-tumour activity in laboratory studies. One molecule, called ananain, blocks a cancer causing protein called Ras, which is defective in approximately 30% of all cancers. The other molecule, called canizain, stimulates the bodies own immune system to target and kill cancer cells. The proposed research seeks to provide proof of concept of the use of ananain and canizain as drug development targets. Once this early proof of principle phase has been completed, we believe that ananain and canizain would be extremely attractive targets for further investment by a major pharmaceutical company.Read moreRead less
Development Of Novel And Selective Anticancer Drugs Derived From Cysteine.
Funder
National Health and Medical Research Council
Funding Amount
$264,250.00
Summary
In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tum ....In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tumour drugs that possess unusually high selectivity in acting on cancer cells without killing normal human cells. Our current proof of concept will be turned into a drug development candidate that will improve our negotiating position with commercial partners.Read moreRead less