Anaphylaxis: Pathophysiology, Acute Management, Diagnosis And Immunotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. This award will support research projects that aim to improve both the emergency care of this condition and subsequent immunotherapy (desensitisation) for people who experience anaphylaxis to insect sting. It will also support research to better understand anaphylaxis to antivenoms, which is a major problem worldwide, and to thus improve the treatment of snake, scorpion and spider envenoming.
Mimotopes For The Investigation And Therapy Of Allergic Disease
Funder
National Health and Medical Research Council
Funding Amount
$203,296.00
Summary
10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable ....10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable immunotherapy which, like vaccines use few injections. Mimotopes provide a new opportunity. Studying the parts of the allergens recognized by the immune system (epitopes) can reveal important phenomena undetectable with whole allergens; and single epitopes may be a powerful avenue to effective immunotherapy. The therapy can be targeted to a selected arm of the immune system for maximal effect and the immediate side effects induced by cross linking antibodies with two epitopes can be avoided. Allergens interact with two types of lymphocyte, the T and B cells. T-cell epitopes can be easily studied because they comprise short regions of proteins which can be synthesized. B-cell (and antibody) epitopes are shapes formed by the interaction of several parts of a protein which cannot be represented by a simple sequence. The mimotope technology uses random peptides to obtain a shape which mimics the B-cell epitope. Here mimotopes will be produced and used to study the common specificities recognized in allergic responses to house dust mite allergens to develop new types of therapy. Importantly recent information shows that B-cell epitopes can be used to modify both T and B-cell function.Read moreRead less
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
Structure-function Relationships Of Rye Grass Pollen Allergens And Preparation Of Hypoallergenic Mutants For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$223,928.00
Summary
Grass pollen is an important cause of allergy (eg. hayfever, allergic asthma) world-wide affecting up to 30% of the population. In Australia, rye grass pollen is a clinically significant health problem costing $83-160 million per annum. At present, the main treatment of seasonal allergy is by pharmacotherapy with the use of crude extracts in specific immunotherapy which often causes large and annoying local skin reactions and may even cause anaphylaxis. Moreover, the use of crude extracts in dia ....Grass pollen is an important cause of allergy (eg. hayfever, allergic asthma) world-wide affecting up to 30% of the population. In Australia, rye grass pollen is a clinically significant health problem costing $83-160 million per annum. At present, the main treatment of seasonal allergy is by pharmacotherapy with the use of crude extracts in specific immunotherapy which often causes large and annoying local skin reactions and may even cause anaphylaxis. Moreover, the use of crude extracts in diagnosis of allergy among some atopic individuals may be inaccurate or ineffective. In the last eight years of my research, I have contributed significantly to the identification, characterisation and molecular cloning of grass pollen allergens. In this proposal, I aim to evaluate recombinant rye grass pollen allergens as standardised and more effective diagnostic reagents and, through the identification and better understanding of the allergenic segments of these proteins, to prepare recombinant mutants of the same proteins which are no londer allergenic. Avaliability of such non-allergenic protein reagents will provide safer immunotherapy in the future. Moreover, since the biolgical role, function and structure of such allergens in the grass pollen still remain largely unknown, I will aim to investigate this with the clinically significant allergens of rye grass pollen. Determination of biological function and structure of such allergens will allow their importance for the pollen-plant to be determined and, since function may be relevant to sensitisation of suceptible individuals to these allergens, these findings will stimulate the development of novel concepts in allergen prevention and therapy.Read moreRead less