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Molecular Dissection Of Allergen Sensitisation And Immunotherapy: Direct Application To Precision Medicine In Treatment Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$1,270,097.00
Summary
Asthma is a major global health burden with huge socioeconomic impact. Most asthmatic patients are allergic. Allergen immunotherapy is the only treatment to alter the natural disease course, but does not work in many treated patients, and robust laboratory biomarkers for patient selection and immune monitoring of treatment success are lacking. Therefore, allergen immunotherapy is not offered to most patients who then rely on medications indefinitely. This research will address these needs.
Phase I/IIa Trials Of A Novel T-cell Epitope-based Peptide Therapy For Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$1,440,000.00
Summary
Peanut allergy affects ~2% of the population and is the major cause of food triggered deaths from anaphylaxis. Typically peanut allergy is lifelong. Currently there is no specific treatment. Our vast experience in immunology for house dust mite and grass immunotherapy allowed us to identify critical components of peanut proteins needed as a safe vaccine to build tolerance to peanut foods. Now we will progress this novel and revolutionary vaccine through early phase clinical trials.
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
Australia has one of the highest asthma rates in the world. In this project we will study how natural regulatory T cells suppress asthma in a mouse model. We will determine where and when interactions between regulatory T cells and allergic T cells occur, and define the mechanisms used by regulatory cells to mediate their suppressive effects. Our findings will aid in understanding why asthma develops and how it may be controlled by the immune system itself.
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
The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis ....The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis and sick building syndrome. Largely due to their diversity and complexity, allergenic fungi have not been well studied and the ways in which individuals vary when inhaling spores is not known. Unlike other allergenic particles, it is unlikely that fungal spores release their allergen as soon as they are inhaled because we have shown in earlier in vitro studies that fungi continue to release allergen over time and this is likely to be the case when they are inhaled. Our laboratory has developed two new techniques that allow us to measure how many spores people inhale and whether they are allergic to them. This study will use these tools to detect and identify the important allergenic fungi involved in domestic and outdoor exposure of asthmatics, the degree of contribution to the total allergen load to which subjects are exposed and identify in what conditions fungi are the causal agents in location-specific symptoms. This study will also investigate allergen production of fungi in situ in the human nose, which will have application in allergic sinusitis and asthma amongst other respiratory diseases. We will investigate how readily allergenic spores germinate in the nose and under what conditions they release allergen.Read moreRead less
Improving Immunotherapy By Vascular Targeting And Barrier Alteration
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Tumors grow in part because they escape destruction by the immune system. New blood vessels grow inside tumors by a process called angiogenesis, which then stops cancer-fighting cells in their tracks. We hypothesise that breaking down the blood-tumor barrier will open tumors for attack by the cancer-fighting immune system. This proposal continues our work on reversal of angiogenesis in the context of immunotherapy. We expect these findings to lead to highly effective anti-tumor therapies.