Understanding The Development Of Humoral Immunity To Malaria Merozoites
Funder
National Health and Medical Research Council
Funding Amount
$642,804.00
Summary
We will examine the acquisition of antibody responses to various P. falciparum surface antigens and their association with reduced risk of re-infection and symptomatic malaria in a treatment re-infection study of children from a malaria endemic area of Papua New Guinea. The effector mechanisms by which protective antibodies control parasite burden will be idendify. Defining the antigenic targets and effector mechanisms of immunity is essential for developing anti-malarial vaccines.
A Novel Approach To Identify The Specific Antibody Characteristics Important For Protection From Malaria In Pregnant Women
Funder
National Health and Medical Research Council
Funding Amount
$1,011,223.00
Summary
Antibody protects against malaria, but the specific characteristics of protective antibody are unknown. Pregnant women lack antibody to parasite protein called VAR2CSA, explaining their malaria susceptibility. Using samples from vaccine trials and clinical studies in pregnant women, and a ‘Systems Serology’ approach, we will determine which naturally-acquired or vaccine induced antibodies protect pregnant women from malaria, and how variation in VAR2CSA sequences affects this protection.
Surface Antigens Of Plasmodium Falciparum-infected Erythrocytes And Immunity To Malaria In Humans
Funder
National Health and Medical Research Council
Funding Amount
$599,180.00
Summary
Malaria is a leading cause of death globally, particularly among children. Malaria parasites infect red blood cells and multiply inside them, resulting in severe illness if left untreated. Effective treatments are limited and currently there is no vaccine. In human studies, we aim to identify the target antigens of immune responses and immune mechanisms that protect against malaria. With this knowledge, vaccines can be designed against malaria to prevent serious illness and death.
Antibodies To The Invasion Ligand EBA175 And Protection From Plasmodium Falciparum Malaria
Funder
National Health and Medical Research Council
Funding Amount
$407,792.00
Summary
Malaria causes disease and death by invading into human red blood cells and it achieves this by using specific parasite proteins. One of these, erythrocyte binding antigen 175 (EBA175), is especially important and parasites have evolved different versions of the protein. This project seeks to understand the importance of these different EBA175 variants in evading antibody responses. This has important implications in understanding natural immunity but also for future vaccine development.
The major objective of this research is to advance the development of highly effective malaria vaccines through i) defining mechanisms and targets of human immunity to malaria to establish a rational basis for vaccine design; ii) advancing the development of lead candidates and promising new candidates and combinations; iii) advancing vaccine platforms that induce potent protective immune responses; iv) develop and validate urgently-needed immunological assays for vaccine development and testing
Human Malarial Immunity And Assessment Of Emerging Artemisinin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$312,570.00
Summary
Resistance to antimalarial drugs is a major global threat for malaria treatment, control and elimination. Assessment of the spread of resistance is severely impeded by the presence of host immunity. This project will identify population biomarkers of immunity during antimalarial treatment to include in studies of antimalarial resistance. These findings will facilitate the correct assessment of the global spread of antimalarial resistance.
In Africa, Plasmodium falciparum malaria and HIV infection are devastating health problems, and HIV makes malaria worse, especially in pregnancy. Recently, we showed why this may be. In pregnancy, antibodies to proteins expressed on the surface of malaria infected cells protect against malaria in the placenta. Levels of these antibodies were decreased by HIV infection, and lowest in women with AIDS. Both first-time and experienced mothers lacked antibody. Now we will investigate the function of ....In Africa, Plasmodium falciparum malaria and HIV infection are devastating health problems, and HIV makes malaria worse, especially in pregnancy. Recently, we showed why this may be. In pregnancy, antibodies to proteins expressed on the surface of malaria infected cells protect against malaria in the placenta. Levels of these antibodies were decreased by HIV infection, and lowest in women with AIDS. Both first-time and experienced mothers lacked antibody. Now we will investigate the function of these antibodies. They might block adhesion to placental receptors, decreasing parasite numbers in the placenta. Or they might coat infected red cells, making them targets for phagocytosis (eating) by macrophages (white blood cells). We will examine the effects of HIV on each process, to find out how reduced antibody might affect the pregnant woman. HIV also affects macrophages and related immune cells, monocytes and dendritic cells. We will study how HIV infection in these cells impairs the way they eat malaria cells, and whether it alters the way they become activated and produce infection-fighting proteins when they encounter malaria. Without these proteins, malaria may grow unchallenged. Using our new assays we will study these responses in African women. We will discover whether HIV also affects antibodies to proteins expressed by parasites infecting children, who are at highest risk of malaria. HIV particularly decreases development of antibody to new targets, so children with little malaria experience may lack antibodies to many different proteins. We will find out whether low levels of malaria antibody in children may be the reason why the get more severe malaria. By understanding how HIV affects malaria immunity, we can develop better ways to protect people at risk from malaria. These findings will also be important to work on malaria vaccines. If HIV infected people respond poorly to natural infection, they may also fail to respond to vaccines.Read moreRead less
Apical Membrane Proteins As Targets For A Schistosomiasis Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$480,459.00
Summary
Schsitosomiasis is a chronic neglected tropical disease for which there is currently no vaccine. A vaccine is sorely needed to control this parasite. This proposal seeks to identify molecules from the outer surface of the parasite which are recognised by the immune system of people from Brazil who are resistant to schistosomiasis. Molecules identified in this manner will be tested as vaccines in an animal model of schistosomiasis, and ranked based on their performances to enter human trials.
Transcriptome Profiling Of The Human Pathogen Schistosoma Japonicum
Funder
National Health and Medical Research Council
Funding Amount
$257,560.00
Summary
The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different g ....The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different genes, and to determine where and when they are active, thus placing the mass of data generated by genome sequencing programs into a biological and functional context. Microarrays provide a unique, cutting-edge, tool for investigating schistosome biology. We have fabricated a microarray representing some 20,000 schistosome genes. We will use this resource to perform large scale monitoring of schistosome gene expression during the parasite's complex life cycle, targetting the regionally important Asian schistosome, Schistosoma japonicum, for study. This will provide the single largest insight into the genetic changes that occur during schistosome development, will greatly further our understanding of the adaptations needed for the growth, development and survival of the parasite, and will identify genes involved in key biological processes, all of which may be exploitable for future interventions and treatments.Read moreRead less