Mimetics Of Natural Triggers Of Innate Immunity As Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. ....Knowledge of what properties of an antigen allow it to induce an immune response is central to our understanding of how we fight disease and how we can vaccinate effectively against disease. The fact that an antigen is foreign to the host is not in itself sufficient for it to initiate the series of events that must take place in order to activate B and T lymphocytes, the cells involved in immunity. For vaccine purposes, antigens must be delivered with substances called adjuvants to be effective. There is very little known about how adjuvants actually work but many of the highly effective experimental adjuvants contain an immunostimulant which is usually either whole dead bacteria or components of the cell walls of bacteria or other organisms. From evidence emerging in the literature and our own experimental observations, we have begun to understand the requirements for and the chain of events leading to immune response induction. The interaction of certain lipid-containing groups, present on antigens from pathogenic organisms, with a specialised type of cell, the dendritic cell, is a key event in this process. We have designed synthetic mimics of lipid-containing moieties from bacteria and coupled them to unrelated parts of viral proteins. We showed that these lipopeptides can elicit potent anti-viral immune responses and long lived memory responses. The experiments outlined in this proposal will examine the interaction of these and other second generation lipopeptides with dendritic cells. We will determine whether these can bind to particular molecules on the dendritic cell surface to initiate a specific series of signals leading to immune induction and if so we will seek to use different lipid groups to trigger the immune response in different and predictable ways. The outcomes of this work may have a major impact on the design of new vaccines as well as increase our understanding of how the immune system is triggered to respond to invading organisms.Read moreRead less
Utilising Circulating Tumour DNA (ctDNA) To Optimise The Adjuvant Therapy And Follow-up Of Patients With Locally Advanced Rectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,316,682.00
Summary
The management of patients after surgery for rectal cancer presents multilpe dilemmas; what treatment should be given and to which patients? Our initial studies in colorectal cancer patients demonstrate that a novel blood biomarker (circulating tumour DNA) can accurately predict patient risk of recurrence and with serial samples, can indicate whether chemotherapy is being effective. During follow-up changes in this biomarker promise to be a specific and very early indicator of cancer recurrence.
Engineered Spiky Silica Nanoparticles As Effective Immune Adjuvants By Activating Inflammasome And Enhancing Cellular Uptake
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Vaccination is a triumph of preventative healthcare in Australia and worldwide. Despite substantial advances in vaccine development, some of the most lethal diseases still lack effective vaccines. This project aims to generate a novel immune adjuvant with excellent safety to promote antigen immunity by rationally designing surface structure of nanomaterials. Successful completing of this project has great potential to bring new, safe and potent vaccines for some infectious disease and cancer.
Towards Evidence-based Use Of IVF Add-ons In Australia
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
A large number of extra ‘add-on’ treatments are available which claim to increase the chance of success of IVF. However, there is no evidence that these add-ons are safe or effective, and they can cost patients up to $2000. I will undertake research to measure use of add-ons in Australia and the factors that drive supply and demand. I will use this information to develop resources based on robust evidence which will help guide patients and clinicians in making decisions about using IVF add-ons.
Multistage Vaccines For The Prevention Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$884,290.00
Summary
Almost two million people die from tuberculosis (TB) each year. The current vaccine, BCG, is ineffective at controlling TB and the type of immune response needed to protect against the disease is poorly understood. We have discovered new antigens of the TB bacterium, and we will combine them with novel delivery strategies to develop new TB vaccines. We will also determine the type of immune response needed to protect against TB, which will aid progression of vaccines into clinical trials.
Personalisation Of Aspirin Adjuvant Therapy In Patients With Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$762,580.00
Summary
Aspirin use is associated with a reduced risk of bowel cancer recurrence. However, benefit appears limited to a subset of patients, and some individuals experience side effects. We will analyse tumour samples from patients participating in the ASCOLT clinical trial of aspirin to identify molecular features that can predict who will benefit from aspirin. Predictive biomarkers would be of substantial clinical utility for guiding treatment, minimising toxicity and improving disease outcomes.
The OUTBACK Trial - The Role Of Adjuvant Chemotherapy In Locally Advanced Cervical Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,472,782.00
Summary
This international randomized phase III trial will test the value of giving additional chemotherapy treatment to women with locally advanced cervix cancer following standard chemo-radiation treatment. The aim is to improve survival rates for these women, many of whom have a 40% or greater chance of their disease relapsing after treatment. The trial has been designed in Australia, and is open in multiple countries with Australia New Zealand Gynaecological Oncology Group (ANZGOG) as the lead group ....This international randomized phase III trial will test the value of giving additional chemotherapy treatment to women with locally advanced cervix cancer following standard chemo-radiation treatment. The aim is to improve survival rates for these women, many of whom have a 40% or greater chance of their disease relapsing after treatment. The trial has been designed in Australia, and is open in multiple countries with Australia New Zealand Gynaecological Oncology Group (ANZGOG) as the lead group.Read moreRead less
Hendra virus (HeV) cause a disease transmitted from bats to horses which in turn infect humans and other horses. There are no drugs or vaccines for HeV. Since humans are infected by inhalation, a vaccine that can generate antibody in the lung and protect from infection will be ideal. We have found that a natural sugar called mannan used with virus proteins and administered via the nostrils to generate such responses. In this project we will prepare this vaccine and use it in a mouse model of HeV ....Hendra virus (HeV) cause a disease transmitted from bats to horses which in turn infect humans and other horses. There are no drugs or vaccines for HeV. Since humans are infected by inhalation, a vaccine that can generate antibody in the lung and protect from infection will be ideal. We have found that a natural sugar called mannan used with virus proteins and administered via the nostrils to generate such responses. In this project we will prepare this vaccine and use it in a mouse model of HeV infection to see if it can protect the mice.Read moreRead less
Enabling Technologies For Design And Delivery Of Novel Vaccines Against Infectious Diseases And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$925,346.00
Summary
This grant will support research necessary to develop the next generation of vaccines. These will combat diseases caused by bacteria and viruses and can also be used to fight cancer. The broad range of application is made possible through the incorporation of simple molecular features that activate the immune system. The intellectual property that has been developed is protected by a patent portfolio some patents of which are already licenced to the pharmaceutical industry.