Impact Of Pneumococcal Vaccination And Environmental Factors On Pneumococcal Carriage And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$455,872.00
Summary
Pneumonia is the leading killer of children <5y of age worldwide, and the pneumococcal bacterium is a common cause. Pneumococci are carried in the noses of healthy children. In this project we will determine 1) whether carriage can be used to monitor the impact of vaccination in resource-poor settings, 2) the effect of new vaccines on ear disease and transmission using infant mouse models and 3) if exposure to smoke effects the ability of pneumococci to cause disease and altered gene expressi ....Pneumonia is the leading killer of children <5y of age worldwide, and the pneumococcal bacterium is a common cause. Pneumococci are carried in the noses of healthy children. In this project we will determine 1) whether carriage can be used to monitor the impact of vaccination in resource-poor settings, 2) the effect of new vaccines on ear disease and transmission using infant mouse models and 3) if exposure to smoke effects the ability of pneumococci to cause disease and altered gene expression.Read moreRead less
Treatment Of Chronic Proteinuric Renal Disease With DNA Vaccines Against TCR Subsets Of Effector T Cells And Chemokines
Funder
National Health and Medical Research Council
Funding Amount
$282,750.00
Summary
Current treatments for chronic kidney disease are non specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. This project will develop and test a novel therapeutic strategy of DNA vaccination targeted specifically at groups of white cells, and specific regulatory mo ....Current treatments for chronic kidney disease are non specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. This project will develop and test a novel therapeutic strategy of DNA vaccination targeted specifically at groups of white cells, and specific regulatory molecules in order to prevent chronic kidney disease (CPRD). In chronic kidney diseases of all types, the kidney filters and surrounding tissue becomes infiltrated with inflammatory cells. The amount of inflammation in the filters and the tissues has an important bearing on the severity of kidney failure, and the rate at which kidney disease progresses. There are a range of different cells that invade the inflamed kidney, some worsen the disease while some may protect against it. Current treatments are non-selective and may, by suppressing inflammation, prevent both repair and protection. We have established a central role for two groups of white cells called macrophages and T lymphocytes in two animal models of kidney disease. In one of these models, we used DNA vaccination, which represents a novel means of switching off these disease-causing T cells. The results showed that DNA vaccination against T cell subsets was protective in our model. This raises the real and exiting possibility that DNA vaccination directed at specific disease-causing cells, and their products are much more likely to be specific and effective therapy for chronic kidney diseases. Eventually, such DNA vaccination may be used as a more effective and safer therapy for human kidney disease.Read moreRead less
Combination Antiviral And Immune Therapies For Hepatitis B Virus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Hepatitis B virus (HBV) causes acute and persistent (chronic) infection with varying degrees of liver damage and a strong association with the development of liver cancer. Worldwide ~ 250 million people have persistent HBV infection and while a HBV vaccine is available that protects against infection, current treatments for existing infection are largely ineffective. We wish to study a combination of antiviral drug therapy and vaccination with DNA vaccines, to develop new treatment protocols for ....Hepatitis B virus (HBV) causes acute and persistent (chronic) infection with varying degrees of liver damage and a strong association with the development of liver cancer. Worldwide ~ 250 million people have persistent HBV infection and while a HBV vaccine is available that protects against infection, current treatments for existing infection are largely ineffective. We wish to study a combination of antiviral drug therapy and vaccination with DNA vaccines, to develop new treatment protocols for persistent hepatitis B virus (HBV) infection. The human HBV is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Therapies will be tested in ducks infected with the duck hepatitis B virus (DHBV) as these animals provide the only model system available in Australia for development of HBV therapies. DHBV-infected ducks will be treated with a new and extremely potent antiviral drug Entacavir (ETV; Bristol-Myers Squibb). Drug treatment will be combined with various DNA vaccination protocols, including new strategies that involve DNA vaccine priming and recombinant fowlpoxvirus (rFPV) boosting of immune responses. Inoculation of DNA vaccines and rFPV results in expression of viral proteins that are presented to the immune system and evoke strong immune responses. 'Prime boost' protocols with DNA vaccines and rFPV have shown promise for protection against and treatment of human immunodeficiency virus (AIDS virus) infection. We will assess the effect of treatment by measuring levels of DHBV in liver and blood, clearance of infected cells and serological changes. The ultimate aim is to develop successful therapies that can then be applied to treatment and elimination of HBV infection in humans.Read moreRead less
DNA Vaccination Using Chemokine And Costimulatory Pathways As A Treatment For Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$450,390.00
Summary
Chronic kidney disease (CKD) is a great burden on Australia. Treatments are mostly ineffective. Our DNA vaccination against mediators of inflammation can protect against CKD. On the basis of ongoing studies we have identified 5 candidate molecules involved in recruitment and activation of inflammatory cells. We outline studies to generate DNA vaccines to these molecules, enhance their efficacy, and test them in models that represent the 3 most important causes of human CKD.
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.