Development Of A Novel Mannan-based Avian Influenza Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$195,566.00
Summary
We have a sugar (mannan) that can be used to increase immune responses. We have found that mannan decreases the dose of inactivated virus needed for intranasal immunization. We will investigate if dose sparing is seen when given intramuscularly. This method will be first tried with the human flu virus and if successful will be tried with the bird flu virus. If the preparation can protect mice and ferrets from human or bird flu infection it could develop into a human vaccine against bird flu.
Development Of A Vaccine For Genital Chlamydial Infection
Funder
National Health and Medical Research Council
Funding Amount
$207,551.00
Summary
Genital Chlamydia infections are the most common sexually transmitted infection in Australia with annual health costs of 90-160 million dollars. Infection rates in 15-29 olds are increasing at 15-20% per year. Antibiotics are currently the treatment of choice, however antibiotic resistance is increasing and most infections are asymptomatic and not treated in the absence of screening programs. This project aims to develop a genital Chlamydia vaccine using a combination of novel antigens.
Oxidised Mannan As A Novel Adjuvant To Vaccinate Against Mucosal Infections
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
Most pathogens invade via the mucosal surfaces. However, current vaccines, which are delivered by injection, are poor at inducing mucosal immunity. An ideal vaccine would comprise a defined protein antigen combined with a suitable adjuvant which could be administered intranasally or orally. Protective antigens have been defined for a number of infections but suitable adjuvants have been elusive. We showed that mannan, a complex carbohydrate from yeast, oxidatively linked to protein antigens can ....Most pathogens invade via the mucosal surfaces. However, current vaccines, which are delivered by injection, are poor at inducing mucosal immunity. An ideal vaccine would comprise a defined protein antigen combined with a suitable adjuvant which could be administered intranasally or orally. Protective antigens have been defined for a number of infections but suitable adjuvants have been elusive. We showed that mannan, a complex carbohydrate from yeast, oxidatively linked to protein antigens can be used as an adjuvant for mucosal IgA and other classes of antibody. Given to mice intranasally, antigen coupled to mannan markedly enhanced production of IgA, IgG1 and IgG2a in serum, and IgA in lung, tears, vaginal secretions, saliva and gut. We have confirmed this for a number of known or putative protective antigens. In addition, both the Th1 and Th2 arms of the lymphocyte response were activated. We have demonstrated protection against P. gingivalis (cause of periodontitis and associated with premature birth and cardiovascular disease) in a mouse lesion model. However, before commercial interests will commit themselves, we need to demonstrate protection against viral infections and in other sites like lungs and gut. Three infection models where IgA has been shown to protect are already set up and can realistically produce results in 1 year. 1. Rotavirus is the major cause of severe infantile gastroenteritis in humans and animals world wide. The latest (live) vaccine was withdrawn because of side effects. We have established a model with Simian rotavirus causing an acute self-limiting disease in infant mice. Adult females will be immunised with mannan linked to killed virus preparations, mated and passive protection of their offspring will be assessed. Preliminary evidence links rotavirus infection with the onset of type 1 diabetes. If this is confirmed, there will be an opportunity to test the vaccine against diabetes. 2. Influenza: IN infection of mice with flu virus is a well established model. Mice will be immunised IN with mannan coupled to haemagglutinin-neuraminidase purified from egg-grown virus. They will be challenged IN with influenza virus and virus titrated in lung homogenates. Neutralising antibody in serum and lung washings will essayed. 3. Respiratory syncytial virus: RSV is the commonest cause of bronchiolitis and pneumonia in infants for which there have been unsuccessful attempts to produce a vaccine. F and G membrane glycoproteins have been shown to protect mice against IN infection, and they will be used coupled to mannan to vaccinate mice against intranasal challenge.Read moreRead less
Therapeutic Development Of A Novel EphA4 Antagonist For Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$687,105.00
Summary
Spinal cord injuries impose a significant burden on patients and their carers. At present, there are no treatments for spinal cord injury that provide functional improvement. This research program will develop a novel therapeutic molecule, EphA4-Fc, which promotes axonal regeneration and delivers significant functional improvement. We will determine the most effective protocol for EphA4-Fc administration and the physiological and functional outcomes of these treatment regimes.
Elastaderm: An Improved Human Skin Substitute For Treating Burns
Funder
National Health and Medical Research Council
Funding Amount
$326,316.00
Summary
We will focus on proof of concept needed for the commercialisation of improved dermal replacements designed to repair severe skin burns. These novel dermal replacements are a substantial development of and improvement beyond existing technology because they are intended to reduce wound contraction and increase elasticity.
Development Of Monoclonal Antibody Therapy For Treating Wounds
Funder
National Health and Medical Research Council
Funding Amount
$573,354.00
Summary
Chronic wounds, diabetic ulcers, injuries in response to trauma, burns and scalds form a medical need which will only expand as the population ages and the diabetic epidemic grows. In our studies, we have shown that Flightless I (Flii), an actin-remodelling protein, is a negative regulator of wound healing. We are developing monoclonal antibodies as a new therapy for reducing Flii levels in wounds which leads to improved wound repair outcomes.
Neuropathic Pain Drugs Based On The Endogenous Opioid Peptide Endomorphin 1.
Funder
National Health and Medical Research Council
Funding Amount
$209,470.00
Summary
We have developed a new pain drug based on the natural pain killing opioid peptide, Endomorhin 1. The new drug exhibits activity similar to morphine and gabapentin against neuropathic pain in animals but seems to act through a different mechanism. We will complete our preclinical investigation of this compound by assessing its side effect profile and tolerence inducing properties in animals. We will also continue our development of an orally active analogue of this important peptide.
Development Of Flightless Antibody Therapy For Treating Wounds
Funder
National Health and Medical Research Council
Funding Amount
$194,071.00
Summary
Chronic wounds, diabetic ulcers, injuries in response to trauma, burns and scalds form a medical need which will only expand as the population ages and the diabetic epidemic grows. In our studies, we have shown that Flightless I (FliI), an actin-remodelling protein, is a negative regulator of incisional wound healing. We are now developing a new antibody therapy to reduce FliI levels in wounds thereby leading to improved wound repair outcomes.
Commercialisation Of A Glycoprofiling Diagnostic Kit And Novel Therapies For Biofilm Related Respiratory Disorders
Funder
National Health and Medical Research Council
Funding Amount
$203,050.00
Summary
Our preliminary studies have shown that a group of patients who suffer from chronic inflammatory disease and have bacterial biofilm identified on their mucosa have worse outcomes even after surgery. We have shown that they lack certain small protein and sugar molecules on their respiratory lining. We aim to use this technology as a diagnostic tool to aid the doctor in prescribing the appropriate treatment for these patients to prevent bacteria regrowing in their respiratory tract.
Studies Of Metabolites Of Synthetic Flavonols For The Treatment Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$207,440.00
Summary
Cardiovascular disease, including heart attack and stroke, is the leading killer of Australians. A promising new drug, NP202, can reduce the amount of tissue damaged from a heart attack; however, its mechanism of action remains obscure. NP202 is metabolized to a range of compounds, one of which is partly responsible for its beneficial effects. In this project we will identify other metabolites of NP202 and characterize their biological activity to gain insight into its mechanism of action.