Couch Grass Allergy: Cellular And Molecular Studies Directed At Improved Specific Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Couch grass pollen is increasingly important in Australia and other temperate and subtropical regions as a seasonal allergen causing asthma and hay fever. In our allergy clinic 85% of patients with seasonal asthma and-or hay fever are allergic to both couch grass pollen and rye grass pollen. Standard allergy treatment shots usually cover the rye grass pollen allergens but there is no cross-reactivity with couch grass pollen and therefore symptoms due to couch grass pollen are not controlled. The ....Couch grass pollen is increasingly important in Australia and other temperate and subtropical regions as a seasonal allergen causing asthma and hay fever. In our allergy clinic 85% of patients with seasonal asthma and-or hay fever are allergic to both couch grass pollen and rye grass pollen. Standard allergy treatment shots usually cover the rye grass pollen allergens but there is no cross-reactivity with couch grass pollen and therefore symptoms due to couch grass pollen are not controlled. These shots are seldom used in asthmatic patients because of the risk of severe asthma or generalised allergic reactions. We plan to examine human blood cell responses to couch grass pollen allergens before and after allergy shots with a preparation that includes couch grass pollen and rye grass pollen. A comparable control group of patients receiving only drug therapy will also be investigated. This study will identify dominant sites of couch grass pollen allergen immunoreactivity and reveal mechanisms of desensitisation. Based on this information, we will develop novel couch grass pollen proteins that retain the positive features needed for a successful desensitising vaccine but without the ability to bind to allergy antibodies and possibly cause severe adverse events such as asthma attacks. These preparations could be used to provide safer and more effective allergy treatments that can be used in hay fever sufferers and asthmatics.Read moreRead less
The Impact Of Micropolymorphism Within The T Cell Receptor Genes And Their Target Antigenic Peptides
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific T cell receptors (TCRs). This project will investigate the importance of genetic variation in the TCR genes in influencing how we fight infections. Another aim is to examine how the immune system tolerates genetic variation in an infecting virus. Advances in these areas will aid in the development of new "intelligent" vaccines.
CONTAINMENT OF THE T-CELL RESPONSE TO GLUTEN IN COELIAC DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$324,270.00
Summary
Coeliac disease affects about 1% of Casucasians and West Asians, about 250,000 Australians. Diagnosis of coeliac disease is problematic, less than one fifth of Australians with coeliac disease have been diagnosed, while many more adopt a gluten free diet and strictly avoid foods made from wheat, barley, rye and oats mistakenly thinking that they have coeliac disease. New diagnostics and therapies that are easy to perform and acceptable to patients are badly needed if the public are to benefit fr ....Coeliac disease affects about 1% of Casucasians and West Asians, about 250,000 Australians. Diagnosis of coeliac disease is problematic, less than one fifth of Australians with coeliac disease have been diagnosed, while many more adopt a gluten free diet and strictly avoid foods made from wheat, barley, rye and oats mistakenly thinking that they have coeliac disease. New diagnostics and therapies that are easy to perform and acceptable to patients are badly needed if the public are to benefit from emerging understanding of coeliac disease. It is an unfortunate mistake that the immune system recognizes and reacts to gluten in people with coeliac disease. The immune cells that sense gluten and damage the intestine, T-cells, detect only very specific short fragments (epitopes) of gluten proteins. Understanding which gluten fragments cause coeliac disease would enable new tests to diagnose coeliac disease, design of non-toxic gluten, and may even allow new treatments that could desensitise the immune system to gluten in the same way that desensitisation therapy works for allergy. Understanding of the gluten fragments causing coeliac disease is improving but it is still incomplete. We have developed a simple test that can pin-point the gluten fragments recognized by any individual with coeliac disease. With the help of volunteers with coeliac disease and a library of fragmented gluten proteins, we will be able to map all the regions of gluten in wheat, barley, rye, and oats that stimulate T-cells. We will find the most potent epitopes that could be used in diagnostic tests, food tests, and desensitisation therapy. Studying individuals with coeliac disease when they eat oats, normally a forbidden food for coeliac suffers yet fewer than 1:4 actually react to oats, will define the changes in intestinal tissue following destructive or tolerant responses to this grain and provide a tool to assess future desensitisation therapies for coeliac disease.Read moreRead less
The Adaptive Immune Response To Epstein-Barr Virus.
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against ....Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against EBV.Read moreRead less
Investigations Into Supraphysiologic T Cell Receptors And T Cell Agonists.
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
T cells are critical in controlling infection and important for the natural eradication of cancer. Through shape recognition, T cells identify dangerous antigens via the surface-bound T cell receptor (TCR). Using new technologies this project aims to "tune up" the strength of this molecular interaction and create a new generation of high affinity TCR and antigens for use as therapeutic and prophylactic drugs in the battle against infectious disease and cancer.
Human CD4+ T-cell Epitope-based Therapeutic For Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$403,121.00
Summary
Peanut allergy affects ~2% of the population and peanuts are the major cause of fatal food-induced anaphylaxis. Peanut allergy usually appears in infancy and persists indefinitely. At present, unlike grass pollen allergy, there is no preventative treatment. Using blood cells from peanut-allergic patients, we will identify the components of major peanut allergens to use in _allergy shots� to develop tolerance on peanut exposure without risking anaphylaxis.
Evolution Of Adaptive Immunity To Gluten In Coeliac Disease.
Funder
National Health and Medical Research Council
Funding Amount
$472,034.00
Summary
Coeliac disease affects 1 in 100 Australians and can cause significant health problems. Under-diagnosis and a difficult, costly treatment (lifelong gluten free diet) are serious clinical issues. The feasibility of simpler diagnostics and therapies in children and adults for coeliac disease depends on whether children and adults react in the same way to gluten. This proposal seeks to determine whether the immune response to gluten changes over time and establish the feasibility of peptide-based a ....Coeliac disease affects 1 in 100 Australians and can cause significant health problems. Under-diagnosis and a difficult, costly treatment (lifelong gluten free diet) are serious clinical issues. The feasibility of simpler diagnostics and therapies in children and adults for coeliac disease depends on whether children and adults react in the same way to gluten. This proposal seeks to determine whether the immune response to gluten changes over time and establish the feasibility of peptide-based applications.Read moreRead less