Optimising Cervical Screening After The Introduction Of HPV Vaccination In Australia: Modelling Of Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$316,089.00
Summary
This research project will aid decision-making about how best to perform cervical screening in Australia after the introduction of vaccination against the human papillomavirus (or HPV). The project will use computer simulation techniques to explore different scenarios for vaccination and screening and to determine the optimal approach. This project involves a group of international collaborators with expertise in a number of areas including cancer epidemiology, screening for cancer, and computer ....This research project will aid decision-making about how best to perform cervical screening in Australia after the introduction of vaccination against the human papillomavirus (or HPV). The project will use computer simulation techniques to explore different scenarios for vaccination and screening and to determine the optimal approach. This project involves a group of international collaborators with expertise in a number of areas including cancer epidemiology, screening for cancer, and computer simulation methods. HPV is the virus responsible for the development of cervical cancer, and clinical trials have demonstrated that HPV vaccines administered to adoloescent girls are very effective at preventing disease that might have led to cancer in the future. However, Australia currently has a very effective Pap smear screening program, and in the first phase after the introduction of vaccination it will be important for women to continue being screened as usual. In the long term, HPV vaccination is expected to reduce the need for Pap smears. The research will involve a very detailed simulation of how HPV is transmitted in the Australian population, and how this will change after vaccination. The simulation will address questions of importance for any future public HPV vaccination program, such as whether males should be vaccinated as well as females. The simulation will also be used to determine the optimal starting age and frequency of Pap smears in the future. The outcomes of the research will be very important for policy-makers. In the long term, this research will ensure that the best recommendations are formulated for the timing and frequency of Pap smears after HPV vaccination is introduced.Read moreRead less
Evaluation Of Primary HPV Testing For Cervical Screening In Australia
Funder
National Health and Medical Research Council
Funding Amount
$701,037.00
Summary
The overall aim of the project is to use simulation modelling to perform a detailed evaluation of new approaches to cervical screening in Australia, taking into account the implementation of the National HPV Vaccination Program. The project involves collaboration between Australian researchers and investigators at the National Cancer Institute USA. We will integrate local and international data to lead the world in understanding how cervical screening should best be performed in the context of H ....The overall aim of the project is to use simulation modelling to perform a detailed evaluation of new approaches to cervical screening in Australia, taking into account the implementation of the National HPV Vaccination Program. The project involves collaboration between Australian researchers and investigators at the National Cancer Institute USA. We will integrate local and international data to lead the world in understanding how cervical screening should best be performed in the context of HPV vaccination.Read moreRead less
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
A Dendritic Cell Subset Targeting Approach For Generating Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$678,492.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
A Dendritic Cell Subset Targeting Approach For Defining Immune Function And Tailoring Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$692,753.00
Summary
Dendritic cells are important sentinel cells of the immune system that orchestrate our immune responses against invading pathogens. There are different types of dendritic cells and they perform different jobs. We have a series of antibodies that can recognise markers on the surface of different dendritic cells populations. We can use these antibodies as homing devices to deliver foreign material to individual dendritic cell subpopulations and thereby manipulate the type of immune response genera ....Dendritic cells are important sentinel cells of the immune system that orchestrate our immune responses against invading pathogens. There are different types of dendritic cells and they perform different jobs. We have a series of antibodies that can recognise markers on the surface of different dendritic cells populations. We can use these antibodies as homing devices to deliver foreign material to individual dendritic cell subpopulations and thereby manipulate the type of immune response generated. Effectively, we aim to tailor immune responses to fight a particular bacteria, virus, parasite, or even cancer cells. The current proposal will extend the number of antibodies we test for their ability to generate tailored immunity. We will examine a number of new molecules for their ability to shuttle foreign material to dendritic cells and their ability to stimulate immune responses. Next, we will test these homing devices as vaccines and their ability to prevent or treat cancer. Our aim is to develop a robust, highly efficient, generic, vaccination approach for cancer immunotherapy.Read moreRead less
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
What's In A Conversation? Discourse Correlates Of Concepts In The Conversational Model Of Psychotherapy
Funder
National Health and Medical Research Council
Funding Amount
$240,952.00
Summary
How and why does therapeutic talk assist people with mental health disorders to change and restore their sense of self? How do psychiatrists read the potential for such change in the discourse of their patients? This collaborative project, between psychiatry and linguistics, investigates the role of language in providing both strategies for change and evidence of change in the Conversational Model of psychotherapy. The project will examine the linguistic patterns that occur in the forms of talk ....How and why does therapeutic talk assist people with mental health disorders to change and restore their sense of self? How do psychiatrists read the potential for such change in the discourse of their patients? This collaborative project, between psychiatry and linguistics, investigates the role of language in providing both strategies for change and evidence of change in the Conversational Model of psychotherapy. The project will examine the linguistic patterns that occur in the forms of talk used by therapists employing the Conversational Model of Psychotherapy, in order to produce a better understanding of certain mental illnesses, and how they can be treated. Specifically, it will: 1. describe, linguistically, four key discourse categories of the Conversational Model that are taken as indicators of progress in patients with Borderline Personality Disorder 2. explain the therapeutic work of such discourse - what is it about these particular language resources that facilitates the observed changes in patients' discourse and mind? 3. assess the stability of key discourse categories of the Conversational Model, and test the ability of a linguistic profile to reliably distinguish between key therapeutic categories as used by different clinicians. The positive effects of Conversational Therapy on incidence of self harm, violence, hospital stays, drug use and self-reported symptoms in this group have been well documented and are especially impressive given that many of the patients in these studies had been turned away from other forms of treatment as unresponsive. By understanding better how this therapy works in a patient group that is typically resistant to treatment but responsive to this particular treatment, we hope to improve health outcomes for people diagnosed with Borderline Personality Disorder. In the longer term we expect this research to help improve techniques for enhancing the mental health of Australians more generally.Read moreRead less
Novel Generic Vaccine Approaches Applied For The Prevention Of Hepatitis C And Influenza Virus Infections.
Funder
National Health and Medical Research Council
Funding Amount
$392,328.00
Summary
For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are maj ....For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are major human pathogens. HCV has infected 200 million people worldwide, and there is no effective vaccine available. Influenza continues to affect thousands of people each year causing epidemics with severe morbidity and considerable mortality. Current influenza vaccines are mostly inactivated formulations and they exhibit poor immunogenicity in immunological naive persons such as children and in the elderly. The influenza vaccines are not optimal for stimulation of cell-mediated immunity. We propose to use particulate antigens as a delivery platform for influenza and HCV-specific epitopes with the focus to develop approaches to target various HCV and influenza strains, including H5N1 bird influenza. We have successfully produced modified VLPs containing HCV-specific sequences, which are able to induce anti-HCV antibodies with neutralising capacity. We hypothesise that the design of VLPs with an appropriate set of HCV-specific antigens will enhance the neutralising capacity of anti-HCV sera and this may overcome strain specificity. This application will exploit a prototype delivery system to induce antibody and also cellular responses against a variety of HCV- and influenza specific target sequences (epitopes). The outcome of this study will be a prototype multivalent vaccine to a range of HCV- and influenza-specific epitopes. As a delivery system this will be ideal for vaccination against agents that are highly variable.Read moreRead less