Neonatal Immunization With Pneumococcal Conjugate Vaccine In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,181,966.00
Summary
One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the dev ....One million children die every year of pneumococcal (Pnc) disease, the majority in the third world. Many die in early infancy and babies may benefit from immunisation with a Pnc conjugate vaccine (PrevenarTM) at birth. The Papua New Guinea (PNG) Insatiate of Medical Research; Telethon Institute for Child Health Research and the Department of Paediatrics, University of Western Australia, will collaborate to closely examine the safety of this approach, particularly with regard to impact on the development of immunity and response to other vaccines given to infants. This study will also provide a unique opportunity for training of PNG and Australian scientists in both countries; transfer state-of-the-art immunological technology and stimulate further collaborations on respiratory infections in the region.Read moreRead less
Dysregulation Of Cytokine Networks: A Key Determinant Of The Pathogenesis Of Cerebral Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$480,989.00
Summary
Malaria is a parasitic disease that kills some 2 million people each year. It affects the Australian region, e.g. PNG and SE Asia. One of the most serious complications is cerebral malaria (CM). It affects the brain and is often fatal. This project will show whether the early meeting of the malaria parasite with the host's immune system determines if the infection will be a mild, resolving one or a severe, possibly lethal one causing CM. This is highly relevant to vaccine development strategies.
Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.
Immune Dysregulation In HIV Patients With Immune Reconstitution After Highly Active Anti-retroviral Therapy
Funder
National Health and Medical Research Council
Funding Amount
$411,000.00
Summary
As HIV infection progresses to AIDS, there is a depletion of CD4 T-cells from the patient's blood and inhibition of the function of the remaining cells. Some immune defects resolve if the patient is given treatment with highly active anti-retroviral therapy (HAART), but it remains to be determined if the function of the imune system returns fully to normal. We have shown that problems with the regulation of the restored immune system in the first 6 months of treatment can lead to diseases associ ....As HIV infection progresses to AIDS, there is a depletion of CD4 T-cells from the patient's blood and inhibition of the function of the remaining cells. Some immune defects resolve if the patient is given treatment with highly active anti-retroviral therapy (HAART), but it remains to be determined if the function of the imune system returns fully to normal. We have shown that problems with the regulation of the restored immune system in the first 6 months of treatment can lead to diseases associated with Mycobacterial infections (eg: tuberculosis), CMV retinitis, hepatitis B virus or hepatitis C virus. We have defined these conditions as Immune Restoration diseases (IRD) and shown that they occur in one in four individuals who begin HAART from low baseline CD4 T-cell counts. IRD are likely to become common as therapy becomes available in Africa and Asia as patients begin treatment from low CD4 T-cell counts. There is also emerging evidence that dysregulated T-cell responses may cause disease later in the course of immune reconstitution. For example, some patients with undetectable HIV experience opportunistic infections or autoimmune disease after many months of HAART. This project will use West Australian patients receiving optimal therapy for their HIV infection. We will analyse immune activation and T-cell function in patients beginning HAART with low CD4 T-cell counts and patients who have had well-controlled HIV infection for at least 6 months. Blood samples will be collected for the measurement of immunological messengers (cytokines) known to be involved in different types of immune responses. The results will be correlated with the clinical outcome.Read moreRead less
Characterisation Of Cell-mediated Immune Responses In Burkholderia Pseudomallei Infection
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and ot ....The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and other parts of the world, and the lack of basic scientific information regarding this disease, has prompted this study. The bacterium lives within the body's cells and therefore does not respond well to standard antibiotic treatment. Although some of the basic immune mechanisms have been identified, how protection to the organism develops remains unclear. In this project we will investigate the effect of B. pseudomallei on immune cells or lymphocytes. This study will determine the patients' immune responses to the bacteria causing the disease. Our research team has already successfully carried out work on several different aspects of melioidosis. The characterisation of the basic immune function determined in the proposed study will provide the scientific basis for improvement in treatment and the development of possible preventive strategies against melioidosis.Read moreRead less
Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients ....Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients with chronic infection are expected to die prematurely due to chronic liver disease or primary liver cancer. Interestingly, exposure to HBV can lead to either acute resolving or chronic HBV infection. Like chronic infections, acute infections involve spread of virus to virtually every hepatocyte, followed by rapid clearance of the virus mediated by the host immune response. Our immediate aim is to study the resolution of acute HBV infections to determine how the stable intracellular viral genome, covalently closed circular DNA (cccDNA), is cleared from the nucleus of infected hepatocytes. Our broad long-term aim is to develop new and effective treatments for chronic HBV infection based on a better understanding of how acute HBV infections are resolved by the host. Based on our previous work we believe that clearance of cccDNA requires hepatocyte death, together with compensatory proliferation of other infected hepatocytes. We will perform detailed studies in duck hepatitis B virus (DHBV) infected ducks to determine if hepatocyte death and compensatory proliferation are essential to clear the infection, or if mechanisms exist for clearance that do not involve cell destruction.Read moreRead less