A Multiple Antigen Lipophilic Adjuvant Carrier (MALAC) System
Funder
National Health and Medical Research Council
Funding Amount
$141,500.00
Summary
We have developed a Multiple-Antigen-Lipophilic-Adjuvant-Carrier (MALAC) system, based on the incorporation of lipoamino acids into a poly-functional core that provides an excellent means for enhancing the antigenicity of a potential peptide vaccine. A system is used for generating antibodies without the use of any conventional adjuvant. The system comprises two or more different antigens and one or more lipid anchor. The key of this system is a novel carrier construct, which is non-toxic and no ....We have developed a Multiple-Antigen-Lipophilic-Adjuvant-Carrier (MALAC) system, based on the incorporation of lipoamino acids into a poly-functional core that provides an excellent means for enhancing the antigenicity of a potential peptide vaccine. A system is used for generating antibodies without the use of any conventional adjuvant. The system comprises two or more different antigens and one or more lipid anchor. The key of this system is a novel carrier construct, which is non-toxic and non-immunogenic. The system contains variables, which allow optimising its structural configuration. A small library of poly-functional MALAC system will be synthesised in a controlled step-by-step way combining solution or solid phase techniques, where the exact chemical structure (and the order of the different immunological peptide sequences) of the construct is pre-determined. The antigenicity and the protection against disease will be compared with antigenicity and protection generated using conventional vaccine carriers. We also aim to exploit the particulate-forming properties of the lipo-peptide amphiphiles, to form micro-particulate oral antigens, exploiting the phenomenon of particulate uptake from the GI tract by the GALT or other intestinal sites. The MALAC constructs will be administered orally followed by the measurement of the serum IgG. 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 of skilled medical personnel, risk of HIV and other blood-born diseases, restricted availability and sometimes, stimulation of the wrong type of immunity. Development of vaccines for oral administration make them much more widely available, permitting self-administration and improving the operation of Public-Health vaccination programs, particularly in developing countries.Read moreRead less
Impact Of Influenza A Infection On T Cell-mediated Immunity To Pulmonary Tuberculosis.
Funder
National Health and Medical Research Council
Funding Amount
$488,058.00
Summary
Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of B ....Tuberculosis is a leading cause of death worldwide and there is an urgent need to develop better anti-TB vaccines. Infection with respiratory viruses may reduce memory T cell responses to M. tuberculosis (Mtb). This project will investigate if Influenza A infection reduces memory anti-tuberculosis T cell responses in mice previously exposed to Mtb or BCG. We will then use influenza viruses engineered to carry parts of Mtb proteins to boost anti-Mtb T cell responses and the protective effect of BCG.Read moreRead less
Autophagy: A New Pathway For Presenting Antigen In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$444,973.00
Summary
Microbes are chopped up and digested before being displayed to the immune system. Here we will investigate a new pathway termed _autophagy� that helps cells to digest material for immune display.
Production Of Interferon Lambda By Dendritic Cell Subsets And Role In Adjuvant Effects Of Poly I:C
Funder
National Health and Medical Research Council
Funding Amount
$396,541.00
Summary
This proposal describes the identification of specific cells in mouse and humans that produce the anti-viral compound interferon-lambda. We propose to further characterise the mechanisms that induce interferon-lambda expression by these cell types and to decipher how this is controlled at the genetic level. We also aim to determine how the production of interferon lambda by these cell types can influence the immune response to viral infection.
The Mechanisms Of Establishing, Maintaining Immunological Memory And Immunodominance Hierarchy
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amoun ....The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amount-length of antigen exposure; and the influence on memory induction from various immune modulators (cytokines) at the time of antigen encounter. Using a range of sophisticated detection methods, very early memory T cells will be identified in the primary response and tracked through their differentiation into long-term memory pool. Experiments will determine how T cells against particular determinants are selected from the primary immune response, retained in the memory pool and recalled in the subsequent challenges. The properties of antigen processing of various determinants will be correlated with the immunodominance hierarchy in the primary and memory response. Taken together the proposed project is central to understanding how memory T cells are created and what rules govern their stability. The project is highly relevant to vaccine design against tumours and pathogensRead moreRead less
Hepatitis C Vaccine Preparedness Study: Investing In Infectious Disease Prevention
Funder
National Health and Medical Research Council
Funding Amount
$820,767.00
Summary
Injecting drug users (IDU) are a key target group for new vaccines designed to prevent hepatitis C virus (HCV) infection. This study will establish the feasibility of conducting HCV vaccine trials in IDUs by answering key scientific questions, generating data to inform trial design and evaluation, establishing a partnership between leading international researchers and the peak Australian body for people who inject drugs, and providing the foundation for a global HCV prevention trial network.
A Randomised Controlled Trial Examining Stability Of New Types Of Highly Porous Surfaced Acetabular Components In Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$216,490.00
Summary
Numbers of total hip replacements are steadily increasing. The most common complication of hip replacement is late implant loosening, which can be predicted by early migration. We will examine early migration of a trabecular metal acetabular cup without screws, compared to a titanium fibre metal acetabular cup fixed with screws. Ideally, an acetabular cup would achieve a level of initial stability by press-fit alone without screws, as screws increase the risk of bone loss around the prosthesis.
The West Nile Viral Protease, NS3: A Target For Antiviral Drug And Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$230,500.00
Summary
The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in the Midd ....The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in the Middle East, parts of Africa and Europe, but recent epidemics in Israel (1998), Romania (1996), United States (1999), and UK (2003) have been characterized by severe symptoms , severe neurological pathology, and fatalities. In the USA alone there were 4,156 infections and 284 deaths in 2002, 9122 infections and 223 deaths in 2003, and this mosquito borne virus has quickly spread since 1999 through all USA states and into Canada and Mexico (http:--www.cdc.gov-ncidod-dvbid-westnile-index.htm). No treatments or vaccines are available. This project focuses on an enzyme, known as the West Nile Virus NS3 protease, that is essential for replication of the virus. By studying the enzyme in the laboratory we can design small molecules that can block its function and these have real potential as leads for development of drug treatments for people infected by this virus. A precedent is the success of inhibitors of HIV-1 protease that are the most effective treatment for humans with HIV-infections. Our studies will also be used to develop potential vaccines. The science involves experts on protease enzymes, drug design and development, virology including West Nile virology, and vaccine development. We expect to generate drug and vaccine candidates and new information for their development that is at the cutting edge of West Nile Virus research.Read moreRead less