A Novel Lipidic Adjuvant Carrier System For Vaccination Including Vaccination Via The Oral Route
Funder
National Health and Medical Research Council
Funding Amount
$214,593.00
Summary
We have developed a Lipid-Core-Peptide vaccine adjuvant system, based on the incorporation of lipoamino acids into poly-functional moiety that provides an excellent means for enhancing the antigenicity of a potential peptide-vaccine. As the system contains many variables, which allow substantial modifications to be made, we now wish to fully optimise its structural configuration. A library of spacer-lipoamino acid-poly-functional multiplier systems will be synthesised on solid phase. Model pepti ....We have developed a Lipid-Core-Peptide vaccine adjuvant system, based on the incorporation of lipoamino acids into poly-functional moiety that provides an excellent means for enhancing the antigenicity of a potential peptide-vaccine. As the system contains many variables, which allow substantial modifications to be made, we now wish to fully optimise its structural configuration. A library of spacer-lipoamino acid-poly-functional multiplier systems will be synthesised on solid phase. Model peptide epitopes will be synthesised on these different lipid-core systems and the antibody response will be compared with the response of the model peptide epitopes coupled to conventional vaccine carriers. The Lipid-Core Immunogen constructs including particulate systems will be administered orally as well, followed by measurement of the serum IgG response and the secretory IgA. This novel system can be used for any potential vaccine-peptide epitope and can open a new route to modern vaccination. The specific advantages of these kind of synthetic vaccines include the greater stability of the vaccine, reproducibility, eliminate the use of toxic conventional adjuvants. The key to this system is a novel carrier construct, which is non-toxic and not immunogenic. The system confers immunity with smaller risk of reaction, since it generates antibody production only against the infective microorganism. Vaccination via the oral route is highly desirable since it can overcome many of the disadvantages inherent in administration by injection - e.g. poor patient acceptability, requirement for skilled medical personnel, risk of HIV and other blood-borne diseases, restricted availability and, in cases, stimulation of the wrong type of immunity. Development of vaccines for oral administration will make them much more widely available, permitting self-administration by patients and markedly improving the operation of Public Health vaccination programs, particularly in developing countries.Read moreRead less
Role Of ABCA8 Transporter In Oligodendroglial Lipid Regulation And Multiple System Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$651,516.00
Summary
Multiple system atrophy (MSA) is a rapid-onset brain disorder impacting on multiple functions of the body resulting in death. The cause of MSA is unknown and there is no cure. In MSA brains, the oligodendroglial cells are impaired and cannot properly make myelin (specialized lipid membrane), which is required for the proper functioning of the nerve cells in the brain. The aim of this project is to find out how changes in lipid in the brain impact on the MSA disease process.
The Role Of Seipin In Lipid Metabolism And Adipogenesis
Funder
National Health and Medical Research Council
Funding Amount
$397,749.00
Summary
The prevalence of obesity and its related disorders has reached an alarming level in Australia and other developed countries. Obesity is characterized by accumulation of fully-differentiated adipocytes loaded with lipid droplets (LDs). Therefore, understanding the cellular dynamics of LDs and the molecular mechanisms of adipogenesis (adipocyte differentiation) is of crucial importance in our battle against obesity. Our proposed study will help undertand the mechnisams of obesity.
Elucidating Metabolic Dysregulation In Alzheimer’s Disease: Profiling The Peripheral Immune Cell Lipidome To Unravel Pathological Mechanisms.
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Both the immune system and lipid metabolism have been identified to be important in Alzheimer’s disease (AD). With the failures of all clinical trials attempting to treat AD, we seek to determine a way to both better diagnose individuals with AD and to identify people at increased risk. This project uses a novel profiling technique to characterise the lipid composition of immune cells to diagnose, predict risk, monitor the disease and to identify potential disease modifying therapeutic targets.
Lipoprotein Metabolism And Mutations Of The APOB Gene Causing Familial Hypobetalipoproteinaemia
Funder
National Health and Medical Research Council
Funding Amount
$396,179.00
Summary
Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and ear ....Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and early atherosclerosis. In contrast, familial hypobetalipoproteinemia is a rare inherited disorder of lipoprotein metabolism characterised by very low levels of cholesterol and apoB in the blood and resistance to atherosclerosis and cardiovascular disease. The focus of this research project is to explore the regulation of apoB metabolism using individuals from unique families with familial hypobetalipoproteinaemia. First, we will determine and characterise the alterations in the APOB gene causing the low cholesterol levels in families with familial hypobetalipoproteinaemia. Second, we will determine if these apoB alterations affect the production and-or clearance of blood fats, or lipoproteins in affected individuals, when compared to controls, by performing metabolic studies. The proposed human in vivo metabolic studies will lead to a better understanding of the mechanism(s) involved in the assembly, secretion, transport, and clearance of plasma apoB-containing lipoproteins. Furthermore, these studies may reveal new protective mechanisms and potentially aid in the development of strategies to suppress over-production of apoB-containing lipoproteins in reciprocal conditions such as familial combined hyperlipidaemia or polygenic hypercholesterolaemia.Read moreRead less