Molecular Approaches To Developing Subunit Vaccines With Improved Efficacy Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to ....Tuberculosis remains a major worldwide health problem, resulting in approximately 3 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. The bacterium that causes tuberculosis is made up of may proteins, some of which are known to induce immune responses in animals and humans. We will produce vaccines that are made from 13 of these important proteins. Using a laboratory animal model that closely mimics human tuberculosis infection, together with sophisticated immunological techniques, we will determine if these vaccines stimulate the right immune response to fight tuberculosis and prevent infection. In addition, we will exploit molecules known to boost immune responses to optimise these vaccines. Further we will study the recently sequenced genome of the tuberculosis bacterium to identify new proteins that may be included in these novel anti-tuberculosis vaccines. This is an internationally competitive project and our team is at the forefront of this research effort. A new, effective tuberculosis vaccine would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Characterisation Of HiaNm, A Novel Outer Membrane From Neisseria Meningitidis; Vaccine Potential And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$356,685.00
Summary
Meningococcal meningitis is a devastating illness which mostly affects children under 5 years. The clinical presentation is of a rapidly progressing disease with high rates of morbidity and mortality. This disease is caused by a bacterium, Neisseria meningitidis (the meningococcus). Vaccines are available against serogroup A and C strains of N. meningitidis, but not for group B strains, which cause the majority of disease in industrialised countries. We have recently identified a gene (designate ....Meningococcal meningitis is a devastating illness which mostly affects children under 5 years. The clinical presentation is of a rapidly progressing disease with high rates of morbidity and mortality. This disease is caused by a bacterium, Neisseria meningitidis (the meningococcus). Vaccines are available against serogroup A and C strains of N. meningitidis, but not for group B strains, which cause the majority of disease in industrialised countries. We have recently identified a gene (designated hiaNm) which encodes a new protein which is located on the surface of the bacterium, in the outer membrane. There has been an enormous body of work done on the immunology, biochemistry and genetics of all components of the outer membrane of Neisseria meningitidis. Therefore the discovery of this novel protein provides an exciting opportunity to take a new direction in vaccine development. For an effective vaccine, the target molecule must be present in most strains; we have already shown that the hiaNm gene is present in all strains examined. In this proposal we describe a study of the vaccine potential and biological function of the hiaNm gene product HiaNm. We will express the protein at high levels, immunise mice, and produce antibodies against HiaNm to discover whether they can protect mice against meningococcal disease. At the completion of this set of experiments we will be in an excellent position to assess the potential for the further development of HiaNm as a component of a meningococcal vaccine.Read moreRead less
Attenuated And Recombinant Mycobacterial Strains As Novel Vaccines To Control Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$370,500.00
Summary
Tuberculosis is a major worldwide health problem. Around one third of the world s population is infected with the bacterium that causes tuberculosis, which results in 2 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. This proj ....Tuberculosis is a major worldwide health problem. Around one third of the world s population is infected with the bacterium that causes tuberculosis, which results in 2 million deaths per year. Furthermore, people infected with the AIDS virus are at a much greater risk of catching tuberculosis. The only vaccine available for tuberculosis, known as BCG, is not very effective at preventing the disease. Therefore there is an urgent need to develop new vaccines to help combat tuberculosis. This project aims to develop and test novel vaccines to prevent tuberculosis. We will produce forms of the existing BCG vaccine that have been altered to boost the components of the immune system needed to provide optimal protection against tuberculosis. Other potential vaccines that we will test are very similar to the bacterium that causes tuberculosis but have been altered such that they do not cause disease. Using animal models of tuberculosis and sophisticated immunological techniques we wish to determine if these live vaccines can stimulate the right type of immune response needed to fight tuberculosis and prevent infection. This is an internationally competitive project and our team is at the forefront of this research effort. A new, effective tuberculosis vaccine would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.Read moreRead less
Chronic Bacterial Infection And The Generation Of T Cell Memory: Implication For Vaccination Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Two million people die from tuberculosis (TB) each year. The immune system is unable to eradicate the TB bacterium, and the type of immune response needed to protect against the disease is poorly understood. We will use animal models of TB infection and sophisticated immunological techniques to decipher how the TB bacterium interacts with the immune sytem and causes disease. We will also develop new TB vaccines that aim to boost the immune response in the lung, the main site of TB infection.
Pathogenesis, Treatment And Prevention Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$9,752,075.00
Summary
Bacterial infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing bacteria and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat bacterial infectious diseas ....Bacterial infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing bacteria and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat bacterial infectious diseases in the 21st centuryRead moreRead less
Development Of A Vaccine For Genital Chlamydia Infections: Protection Against Transmission And Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$322,245.00
Summary
Genital Chlamydia infections are the most common sexually transmitted infection in Australia with annual health costs of 90-160 million dollars. Ifection rates in 15-29 year olds are increasing at 15-20% per year. Antibiotics are currently the treatment of choice, however antibiotic resistance is increasing and most infections are asymptomatic and not treated in the absence of screening programs. The project aims to develop a genital Chlamydia vaccine using a combination of novel antigens.
Regulation Of Pulmonary Immune Responses To Subunit Vaccines Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$509,202.00
Summary
Tuberculosis (TB) remains an enormous health problem world-wide. Improving the effectiveness of anti-TB vaccines is essential for its control. The first approach to improving subunit TB vaccines will be to manipulate the cellular immune response to the vaccine by increasing the positive cytokine signals, or reducing inhibitory effects on the immune response. The second approach is to develop new subunit vaccines to deliver to the lung in order to increase the potency of the protective response.
Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year in developing countries. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Existing pneumococcal polysaccharide vaccines are poorly immunogenic in young children and only provide cover against a limited range of serotypes. S ....Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year in developing countries. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Existing pneumococcal polysaccharide vaccines are poorly immunogenic in young children and only provide cover against a limited range of serotypes. Serotype coverage is even lower in the more immunogenic conjugate vaccines currently being developed; these will also be very expensive, thereby limiting their use in developing countries, where the need for effective paediatric vaccines is greatest. Pneumococci produce a variety of proteins which are important in causing disease, but the relative contribution of these factors at each stage of the infection process remain to be determined. Moreover, virtually nothing is known of the mechanism whereby these virulence factors are regulated in response to the external environment of the bacterium. In view of this, we are conducting a comprehensive examination of the mechanisms of pathogenesis of pneumococcal disease, with particular reference to the role of putative virulence proteins. This information is being used to develop cheap and effective vaccines based on pneumococcal protein antigens common to all serotypes.Read moreRead less
Pathogenesis And Prevention Of Shiga Toxigenic Escherichia Coli Infections
Funder
National Health and Medical Research Council
Funding Amount
$341,320.00
Summary
Shiga toxin (Stx)-producing strains of Escherichia coli (STEC) are known to cause diarrhoea and haemorrhagic colitis in humans. In a proportion of cases, this leads to potentially fatal systemic complications, such as haemolytic uraemic syndrome (HUS), which is the commonest cause of acute renal failure in children. HUS has a high mortality rate in spite of intensive supportive therapy. Morbidity is also substantial, as permanent renal damage and neurological sequelae occur in a significant prop ....Shiga toxin (Stx)-producing strains of Escherichia coli (STEC) are known to cause diarrhoea and haemorrhagic colitis in humans. In a proportion of cases, this leads to potentially fatal systemic complications, such as haemolytic uraemic syndrome (HUS), which is the commonest cause of acute renal failure in children. HUS has a high mortality rate in spite of intensive supportive therapy. Morbidity is also substantial, as permanent renal damage and neurological sequelae occur in a significant proportion of survivors. Large outbreaks of STEC infection are becoming increasingly common, and highlight the threat to public health posed by these bacteria. The serious systemic complications of STEC disease, as well as much of the intestinal pathology, are directly attributable to Stx. However, pathogenesis is multifactorial and capacity of the bacteria to colonize the gut is a crucial virulence trait. STEC infections can now be diagnosed very early in the course of disease, but currently no effective therapeutic intervention is possible. We are addressing this deficiency by developing a novel therapy for STEC infections based on a genetically modified harmless bacterium capable of binding toxin in the gut. Vaccines capable of preventing transmission of STEC disease in the community are also needed, but development of these demands a full understanding of the mechanisms whereby diverse STEC strains adhere to intestinal epithelium and colonize the human gut. We are therefore also examining the interaction between STEC and gut epithelial cells at the cellular and molecular level, with a view to identifying and assessing the vaccine potential of key determinants of adherence.Read moreRead less
Coordinate Expression Of Virulence Factors In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated ....Escherichia coli is a versatile pathogen capable of causing a range of disease types including diarrhoea, dysentery, haemolytic uremic syndrome, bladder and kidney infections, septicaemia, pneumoniae and meningitis. Infections due to pathogenic E. coli may be limited to mucosal surfaces or can disseminate throughout the body. Amongst the different classes of pathogenic E. coli, diarrheagenic strains (namely enterotoxigenic and enteroinvasive E. coli) are responsible for the death of an estimated one million humans per year, mainly in third world countries. The majority (80%) of urinary tract infections (UTIs) in humans are caused by E. coli and in Australia alone there are about 250,000 cases per year. It is estimated that one in four women and one in twenty men will develop a urinary tract infection in their lifetime. Pathogenic E. coli strains are normally equipped with multiple virulence factors and there is mounting evidence that the expression of such factors is finely orchestrated by mutual regulatory cross-talk. For example, expression of flagella (which provide motility) and adhesins (which provide attachment) are fundamentally counteracting phenotypes, yet the molecular and genetic mechanisms that coordinate their expression are unknown. I plan to examine inter-system cross-regulation of bacterial surface structures (namely adhesins, autoaggregaters, capsules and flagella). The aim is to understand on the molecular level how microorganisms orchestrate expression of virulence factors and will have consequences for our understanding of microbial pathogenicity. The strategy outlined may lead to new routes for strain attenuation and perhaps a method for vaccine strain construction. The research will be performed in collaboration with international high profile partners.Read moreRead less