Manipulating Immunity To Mycobacterium Tuberculosis With Novel Vaccines And Immunotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$524,770.00
Summary
Tuberculosis (TB) is an enormous world health problem with 2 million deaths per year and an estimated one third of the world s population infected with the TB bacterium. People who become infected with the bacterium and cannot clear the infection are at great risk of developing TB later in life. Control of TB is confronted with two major problems. First, the only vaccine available for TB, known as BCG, is not very effective at preventing the disease. We do not know why BCG is not an effective va ....Tuberculosis (TB) is an enormous world health problem with 2 million deaths per year and an estimated one third of the world s population infected with the TB bacterium. People who become infected with the bacterium and cannot clear the infection are at great risk of developing TB later in life. Control of TB is confronted with two major problems. First, the only vaccine available for TB, known as BCG, is not very effective at preventing the disease. We do not know why BCG is not an effective vaccine and the type of immune response required to achieve optimal protection against TB is not fully understood. Second, the drugs currently used to treat TB are expensive, treatment times are long and drug resistance is increasing at an alarming rate. Therefore there is an urgent need to develop new vaccines and therapies against TB. We propose to use animal models of TB infection and sophisticated immunological techniques to compare immune responses generated by TB, BCG and new generation vaccines developed in our laboratory. This will allow us to identify the key features of a vaccine that results in effective, long-lasting protection against TB infection. Novel strategies to increase the immune response in the lung, the main site of TB infection, will also be examined. This will involve pulmonary delivery of molecules that increase the number and effectiveness of lung antigen presenting cells, which are necessary to drive the right type of immune response to eradicate the TB bacterium. Increasing lung immunity will be used to either boost the effect of the BCG vaccine, or as a therapy to kill the bacterium in those already infected. This is an internationally competitive project and our team is at the forefront of this research effort. The development of new vaccines to prevent TB or new strategies to treat established TB infection would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Tuberculosis is one of the most threatening infectious diseases worldwide due to the low efficiency of the only licensed anti-tuberculosis vaccine, BCG. This project aims to interrogate two previously neglected immune mechanisms and their potential to enhance vaccine-induced immunity by incorporating these mechanisms into new genetically modified BCG strains. We will also investigate alternative BCG vaccination routes to generate long-lived immune cells that can rapidly control the infection.
Vitamin D And Acute Lower Respiratory Tract Infection (ALRI) In Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$92,669.00
Summary
Australian Indigenous children experience extreme rates of acute lower respiratory infection (ALRI) that medical interventions have failed to reduce. Vitamin D is an important immunoregulatory molecule of the respiratory system that remains uncharacterised in this population. We propose that deficiency contributes to the persistent rates of ALRI. This study will characterise vitamin D levels in a cohort of Indigenous children with and without ALRI. The results will guide future intervention.
Enhancing Host Defence Mechanisms In Severe Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$830,447.00
Summary
New options to treat bacterial infections are needed because of the rapid increase in antibiotic resistance. One very attractive strategy is to boost the body’s own defence mechanisms against bacteria. This project defines novel molecular mechanisms that can be manipulated to better control a bacterial infection. Novel drugs targeting these molecular pathways are already being developed, albeit for cancer. This project will help assess if these drugs may be useful to treat infections.
Glycosyltransferase Effectors From Bacterial Enteric Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$772,600.00
Summary
Many disease-causing microbes subvert host cell defences to establish infection in part by transporting virulence proteins, termed “effector” proteins, into host cells via specialized protein secretion systems. We have discovered a new family of bacterial effectors that modify host proteins with a sugar and thereby inactivate them. Here we will characterise the function of these effector proteins during infection with E. coli and Salmonella.
Understanding Uropathogenic E. Coli-mediated Subversion Of Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$932,536.00
Summary
Urinary Tract Infections (UTI) are one of the most common bacterial infections. Uropathogenic E. coli (UPEC) are the primary cause of UTI and increasingly associated with antibiotic resistance. UPEC use an array of strategies to overcome the innate immune system, which provides the first line of defence against infectious diseases. This project aims to understand how UPEC overcomes innate immunity, with the ultimate goal of devising new approaches for the treatment and prevention of UTI.
Role Of Hypoxia Inducible Factor In Innate Immune Function Against Gram-positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$241,352.00
Summary
Our society is currently facing the rise of drug-resistant pathogens ("superbugs") such as the potentially devastating methicillin-resistant Staphylococcus aureus, or _MRSA�. Recently, a molecule known as HIF has been shown to control the ability of our white blood cells to kill bacteria. This proposal aims to investigate the use of HIF boosting drugs to treat infections. These novel HIF agonists could be used alongside conventional antibiotics to improve infectious disease.
Role Of The Host Fibrinolytic System In Invasive Group A Streptococcal Disease
Funder
National Health and Medical Research Council
Funding Amount
$531,444.00
Summary
The flesh-eating bacterium group A streptococcus (GAS) is estimated to cause 700 million cases of self-limiting disease, and 600,000 cases of serious invasive disease each year. Approximately 25% of invasive infections are fatal. We have shown that GAS are able to hijack the host fibrinolytoc system to cause severe invasive infections. We plan to further examine the details of how this contributes to GAS disease. This research may contribute to the future devlopment of new therapeutics.
Dissecting The Molecular Basis For Emerging Alcohol Tolerance In VRE
Funder
National Health and Medical Research Council
Funding Amount
$836,620.00
Summary
Infections caused by vancomycin resistant Enterococcus faecium (VREfm) are a major and growing problem in health care facilities around Australia. We have observed that VREfm is becoming significantly more resistant to killing by alcohol, probably due the increasing use of alcohol-based hand wash products. This project will identify how VREfm is becoming alcohol tolerant, knowledge that will be used to develop alternative disinfection methods or other intervention strategies to stop its spread.
Anti-sporulation Strategies For Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$651,559.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These strains have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains spread and will provide knowledge that is critical for developing improved strategies for preventing these infections.