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
Aldehyde-modified Antigens For The Immunotherapy Of Adenocarcinomas
Funder
National Health and Medical Research Council
Funding Amount
$284,250.00
Summary
The incidence of breast cancer in women is 1 in 8 and the frequency of other cancers are rising. Even with conventional approaches such as surgery, cytotoxic therapy, radiotherapy and combination therapy only a few cancers are treatable. The development of a cancer vaccine will greatly benefit humanity similar to childhood and adult vaccinations for preventing infectious disease. In this proposal we intend to chemically modify a synthetic protein called mucin 1 (MUC1) which is exprssed on cells ....The incidence of breast cancer in women is 1 in 8 and the frequency of other cancers are rising. Even with conventional approaches such as surgery, cytotoxic therapy, radiotherapy and combination therapy only a few cancers are treatable. The development of a cancer vaccine will greatly benefit humanity similar to childhood and adult vaccinations for preventing infectious disease. In this proposal we intend to chemically modify a synthetic protein called mucin 1 (MUC1) which is exprssed on cells in breast cancer to make it more immunogenic - that is make it look more like a foreign protein so that the immune cells can make antibodies or killer cells that recognise it. These activated cells can now migrate to the tumour sites and kill the invading tumour. In order to do this we are going to introduce mannose, a particular sugar that can bind to important white blood cells and an aldehyde group that can activate immune cells. We will test the effectiveness of the modified proteins in mice to see if they can generate an good immune. If this is satisfactory then we will see if mice are vaccinated with these modified proteins can reject implanted mouse or human tumours. If these experiments are successful further work can be done with human cells and later clinical trials. Any methods developed here will be applicable to other cancers and also infectious diseases.Read moreRead less
Metagenomic Analysis To Determine The Prostate Microenvironment And The Aetiology Of Inflammatory Mediated Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$339,534.00
Summary
Infectious organisms have been implicated in the development of several different malignancies. This project aims to determine if this may also be applicable in prostate cancer and if so, to define which organism/s may be responsible, thus providing targets for improving diagnosis, treatment and prevention strategies. The approach will be to identify DNA in the prostate tumour tissue that is foreign to the �normal� prostate environment and indicative of an invading organism.
Investigation Into The Immunogenicity Of Dendritic Cell-derived Exosomes
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Dendritic cells are essential in immune responses. They have unique capacity to stimulate lymphocytes specific to viruses, bacteria and cancers. They are extremely rare and difficult to isolate. We have developed a method of culture which gives a continuous supply of dendritic cells. Cells produced in our culture also produce a high yield of acellular membranous particles called 'exosomes' which have been previously been very difficult to isolate and characterise. Some preliminary reports sugges ....Dendritic cells are essential in immune responses. They have unique capacity to stimulate lymphocytes specific to viruses, bacteria and cancers. They are extremely rare and difficult to isolate. We have developed a method of culture which gives a continuous supply of dendritic cells. Cells produced in our culture also produce a high yield of acellular membranous particles called 'exosomes' which have been previously been very difficult to isolate and characterise. Some preliminary reports suggest that exosomes can induce or modify immune responses and that they have enormous immunotherapeutic potential. Further study of their clinical application is limited by the difficulty of isolating enough dendritic cells from which to isolate exosomes. This study will involve production and characterisation of exosomes from our unique murine dendritic cell culture system. Exosomes isolated will be assessed in terms of potential for immunotherapeutic treatment of disease such as cancer, viral infection and autoimmunity.Read moreRead less
Informing Vaccination Strategies For Pregnant Women Through Linked Population Health Data
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Vaccination during pregnancy has health benefits for mothers and their infants; however, it is a relatively new area of research, and the immediate and long-term consequences for children are currently not well understood. As part of this fellowship, I plan to conduct research into the long-term health impacts of vaccination during pregnancy. This fellowship will build my career as a perinatal epidemiologist and establish expertise in Australia related to vaccines given during pregnancy.
Asia-Pacific Pneumococcal Disease Control In The Pneumococcal Conjugate Vaccine Era
Funder
National Health and Medical Research Council
Funding Amount
$2,500,000.00
Summary
Pneumonia is one of the commonest causes of childhood death worldwide. PCV is a vaccine that prevents pneumonia but it is costly; and causes an increase in disease from strains which are not in the vaccine. Our CRE will address 2 outstanding issues: when to switch from a 3 to 2 dose PCV schedule to make it more affordable; and create new understanding of the non-vaccine strains’ impact on disease in low- and middle-income countries in the Asia-Pacific region.
Investigating The Altered Landscape Of Enteric Viruses Causing Severe Gastroenteritis In Australian Children Following Rotavirus Vaccine Introduction
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
The rotavirus vaccines were introduced in Australia in 2007, decreasing rotavirus disease. Rotavirus strains naturally evolve during replication, however, high vaccine coverage in the population creates a new environment with different evolutionary pressures where strains not protected by the vaccines may emerge and become dominant. The diminished circulation of rotavirus may create an environment where other viruses capable of causing childhood gastroenteritis may increase.
Links2HealthierBubs: Influenza And Pertussis Vaccine Effectiveness And Safety In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$676,333.00
Summary
Vaccination during pregnancy can offer protection against severe respiratory disease for infants in the first six months of life. For this reason, influenza and pertussis vaccines are routinely recommended during each pregnancy. Unfortunately, little is known about the ‘real world’ effect of both vaccines. We plan to conduct the largest and most comprehensive study to date to evaluate all vaccines routinely recommended in pregnancy in Australia.
Expression Of Malaria Parasite Invasion Associated Proteins In The Sporozoite Novel Vaccination Strategy
Funder
National Health and Medical Research Council
Funding Amount
$202,000.00
Summary
Efforts to develop vaccines against malaria still represent a substantial focus of current research activities. Antigens present in the erythrocytic pathogenic stages of the infection account for the majority of targets investigated for potential vaccines. Experimental vaccines targeting the pre-erythrocytic stages [the sporozoite injected by the mosquito, and the hepatic stage parasite) have encompassed a lesser diversity of parasite antigens]. This is the case despite the fact that experimenta ....Efforts to develop vaccines against malaria still represent a substantial focus of current research activities. Antigens present in the erythrocytic pathogenic stages of the infection account for the majority of targets investigated for potential vaccines. Experimental vaccines targeting the pre-erythrocytic stages [the sporozoite injected by the mosquito, and the hepatic stage parasite) have encompassed a lesser diversity of parasite antigens]. This is the case despite the fact that experimentally induced sterile long-lasting immunity in humans has so far only been achieved through exposure to irradiated sporozoites. The acquisition and maintenance of this immunity depends on the use of invasive sporozoites and on the presence of developmentally arrested hepatic stage parasites.Read moreRead less
Diseases caused by the pneumococcus represent the largest cause of vaccine preventable death in the world today, mainly pneumonia and meningitis. In 2011, 16 developing countries will introduce pneumococcal conjugate vaccines, none in east Asia. Lack of research has been a major barrier to their use in the region. We have established an international centre of excellence in the field and we seek support to extend the capacity of this group and to transfer the technology to Vietnam.