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
Immunological Prevention Of Cysticercosis And Hydatid Disease
Funder
National Health and Medical Research Council
Funding Amount
$510,000.00
Summary
Cysticercosis and hydatid disease are caused by infections with the larval stages of tapeworm parasites. These infections cause substantial morbidity and mortality throughout the world, but particularly in developing countries. They are zoonotic diseases, being transmitted to humans from animals. This project aims to develop practical vaccines to assist with the prevention of both cysticercosis and hydatid disease in humans. The vaccines will be used in the parasites' natural animal hosts, there ....Cysticercosis and hydatid disease are caused by infections with the larval stages of tapeworm parasites. These infections cause substantial morbidity and mortality throughout the world, but particularly in developing countries. They are zoonotic diseases, being transmitted to humans from animals. This project aims to develop practical vaccines to assist with the prevention of both cysticercosis and hydatid disease in humans. The vaccines will be used in the parasites' natural animal hosts, thereby breaking the parasite life-cycle and preventing the diseases being passed to humans. Substantial preliminary research has been undertaken by the applicant, including completion of successful preliminary vaccine trials. This project will optimise the vaccines and complete initial field trials in countries with high rates of disease transmission.Read moreRead less
Population Genomics Of Plasmodium Vivax In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$597,238.00
Summary
Plasmodium vivax malaria is a serious global public health problem that has not received the attention it deserves, despite having serious clinical implications and presenting a major problem for regional malaria control programmes. In a study of people living in a malarious area of PNG, we aim to investigate the diversity of natural parasite populations, to better understand the possible effects of malaria control interventions on transmission and human immunity.
Mechanisms And Targets Of Antibody-complement Interactions That Neutralize Malaria
Funder
National Health and Medical Research Council
Funding Amount
$647,977.00
Summary
Our project aims to identify immune mechanisms that neutralize malaria from the moment of inoculation by a mosquito, before infection can become established to prevent the development of malaria disease. Furthermore, we will discover specific targets of protective immune responses. We expect this project will provide major new advances in our knowledge of human immunity to P. falciparum malaria, one of the world’s most significant causes of mortality and morbidity, and we will use this knowledge
Functional Assays Of Immunity To Malaria In Pregnant Women
Funder
National Health and Medical Research Council
Funding Amount
$578,905.00
Summary
Pregnant women are highly susceptible to malaria due to the adhesion of infected erythrocytes to the placenta. Antibodies to these infected erythrocytes can block their placental adhesion and/or facilitate their clearance by immune cells, improving pregnancy outcomes. We aim at informing vaccine design by better understanding the placental adhesion mechanisms and identifying targets of protective immunity as well as antibody correlates of protection from placental malaria and its consequences.
Helminth Secretomes: From Vaccines To Novel Anti-inflammatory Biologics
Funder
National Health and Medical Research Council
Funding Amount
$938,910.00
Summary
Billions of people in developing countries are infected with parasitic worms, but they have been eradicated from industrialised nations. Humans co-evolved with worms, so their recent removal has deprived us of signals required to keep inflammation in check. My research focuses on worm molecules that can be used to (1) develop vaccines to combat these parasitic infections in developing countries, and (2) as a novel platform of anti-inflammatory therapeutics for use in industrialised nations.
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.
This an integrated program of basic research on antigen discovery and immune mechanisms, and preclinical research on novel vaccine platforms, formulations or delivery systems for the rational design and clinical testing of a next generation vaccine against malaria. This interdisciplinary research fosters strong national and international links and offers the potential for significant economic benefit to Australia.
Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate t ....Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate the mechanism by which the parasite kill these cells, so that novel therapies can be designed.Read moreRead less