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.
The Impact Of Influenza A Virus PB1-F2 Protein On Host Immunity And The Potential For Therapeutic Targeting
Funder
National Health and Medical Research Council
Funding Amount
$317,076.00
Summary
The 1918 influenza virus pandemic resulted in 50 million deaths globally and there is potential for new pandemics, such as the predicted H5N1 Bird Flu . Exact causes of such devastating lethality are not fully identified. Newly discovered influenza A virus (IAV) PB1-F2 protein is present in nearly all highly pathogenic IAVs and promotes virus virulence. This study will further examine the way in which PB1-F2 impacts the host, revealing potential therapeutic targets to lessen disease burden.
Interaction Of Anti-viral IDO And NOS2 In Vivo In A Novel Murine STD Model.
Funder
National Health and Medical Research Council
Funding Amount
$573,629.00
Summary
Sexually transmitted viral diseases (STD) are increasing globally, but we know little of how virus is controlled early in infection. We have shown for the first time in vivo, in our STD model, that during an antiviral immune response, soluble factors turn on an enzyme, indoleamine 2,3-dioxygenase (IDO), to break down and deplete the amino acid, L-tryptophan, starving virus to reduce growth early in STDs. Our project will further define the action and control of IDO in STD.
Investigations Into The Mechanism Of Vaccine- Induced Protection Against The Gastric Pathogen Helicobacter Pylori.
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this ....Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this disease. Vaccination against H. pylori is effective in laboratory animal models. A few vaccines have entered the early phases of clinical trials in human volunteers, however the results have been disappointing. We still do not understand how vaccination leads to killing of bacteria in the stomach, although it is known that antibodies are not responsible. A better understanding of how vaccination works in mice will help the design of vaccines for humans. In a novel approach to study vaccination, the gene expression pattern in the stomachs of immunized mice was analyzed using DNA micro-array technology. In this way we identified several novel genes, and as a result we have developed a new theory for how vaccination might lead to killing H. pylori. We propose that a combination of factors, act together to control H. pylori in the stomach: Leptin, known chiefly as the Obese gene, is a hormone produced by fat cells and controls appetite. Recently leptin has also been shown to influence immune cells (T- cells) in the stomach mucosa. These T-cells in turn send signals to the (epithelial) cells on the surface of the stomach which induces them to produce other proteins; some of which we believe may slow the fast-swimming H. pylori bacteria, and some small anti-microbial proteins (defensins), which are able to kill the bacteria directly by making holes in their membranes. The results of this research will be used to help design better H. pylori vaccines for humans.Read moreRead less
Characterisation Of Cell-mediated Immune Responses In Burkholderia Pseudomallei Infection
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and ot ....The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and other parts of the world, and the lack of basic scientific information regarding this disease, has prompted this study. The bacterium lives within the body's cells and therefore does not respond well to standard antibiotic treatment. Although some of the basic immune mechanisms have been identified, how protection to the organism develops remains unclear. In this project we will investigate the effect of B. pseudomallei on immune cells or lymphocytes. This study will determine the patients' immune responses to the bacteria causing the disease. Our research team has already successfully carried out work on several different aspects of melioidosis. The characterisation of the basic immune function determined in the proposed study will provide the scientific basis for improvement in treatment and the development of possible preventive strategies against melioidosis.Read moreRead less
Comparative Effectiveness Of Vaccine-induced SIV-specific CD8 T Cells
Funder
National Health and Medical Research Council
Funding Amount
$607,797.00
Summary
A HIV vaccine remains elusive. Although killer T cell immunity can provide partial protection from HIV disease, we don't know the best type of killer T cells to induce by vaccination. This project compares multiple HIV vaccine strategies in macaques. We will carefully study the quality of killer T cell immunity induced using novel and cutting-edge assays. We will identify the requirements for effective killer T cell immunity to HIV.
Immunopathological Role Of Monocyte-macrophages In Flavivirus Encephalitis.
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
Viral encephalitis is a life-threatening infection of the brain for which there are no reliable treatments. White cells called monocytes enter the brain from the blood and although important in the immune response that destroys the virus, can also damage the brain. Our work focuses on determining how monocytes migrate into the brain in viral infection, what functions they have once inside the brain, and how to exclude a certain types of monocytes that we have found to be particularly damaging.
Understanding And Controlling Viral Escape In Influenza
Funder
National Health and Medical Research Council
Funding Amount
$433,156.00
Summary
Introduction of a new influenza strain into human circulation leads to a rapid global spread of the virus (e.g. H1N1-09 pandemic) due to minimal antibody immunity. Established T-cell immunity towards conserved viral regions promotes rapid recovery. However, the protective immunity exerts pressure on influenza, leading to "escape" mutations. We will unravel how the viral mutants emerge and propose strategies for T cell-based protective immunity and vaccine design against influenza.