Immunological Prevention Of Hydatid Disease And Cysticercosis
Funder
National Health and Medical Research Council
Funding Amount
$345,340.00
Summary
This project seeks to develop practical vaccines to control the transmission of cysticercosis and hydatid disease. These diseases are caused by infection with the larval stages of tapeworm parasites which have a worldwide distribution and cause substantial human morbidity and mortality. The parasites are transmitted to humans from animals. Methods for control of transmission of infection currently rely on public education and anthelmintic treatment of animals. These measures are often ineffectiv ....This project seeks to develop practical vaccines to control the transmission of cysticercosis and hydatid disease. These diseases are caused by infection with the larval stages of tapeworm parasites which have a worldwide distribution and cause substantial human morbidity and mortality. The parasites are transmitted to humans from animals. Methods for control of transmission of infection currently rely on public education and anthelmintic treatment of animals. These measures are often ineffective and there is an urgent need for new tools to help control transmission of these important diseases. Previous research has shown that the animal hosts of these parasites can be protected from infection by vaccination. Prevention of infection in the parasites' animal hosts has the effect of breaking the parasite life cycle and indirectly removes the source of infection for humans. This project will further develop an existing vaccine against hydatid disease, will develop a new vaccine against cysticercosis and will participate in initial international parasite control campaigns based on application of these vaccines.Read moreRead less
Schistosomes are parasitic flukes that survive in the blood vessels of their human hosts for many years. More than 200 million people are infected in developing countries, and Australian travelers to these regions are often infected. As larval schistosomes mature, they undergo physiological changes in the their outer surface, the tegument, and rapidly become refractory to vigorous immune responses. In the 1960's, researchers proposed that schistosomes evade otherwise destructive immune responses ....Schistosomes are parasitic flukes that survive in the blood vessels of their human hosts for many years. More than 200 million people are infected in developing countries, and Australian travelers to these regions are often infected. As larval schistosomes mature, they undergo physiological changes in the their outer surface, the tegument, and rapidly become refractory to vigorous immune responses. In the 1960's, researchers proposed that schistosomes evade otherwise destructive immune responses by masking their presence through the adsorption of host molecules onto the parasite surface. Intriguingly, most of the molecules adsorbed by the parasite are proteins involved in immune responses, such as MHC and immunoglobulins. In order to understand the molecular basis of schistosome maturation and masking, we recently isolated a protein that binds host IgG-Fc from the surfaces of schistosomes. We hypothesise that masking proteins expressed on the surface of developing parasites interfere with the development of protective immune responses by masking the otherwise susceptible tegument. Moreover, masking proteins are ideal candidate antigens for anti-schistosome vaccines. We now propose to test this hypothesis by identifying schistosome surface proteins that acquire host immune molecules, and isolate the genes encoding these parasite masking proteins. Masking proteins will be identified using protein-based affinity methods and differentially expressed gene- and protein-based methods. Recombinant masking proteins will then be assessed as unmasking vaccines in a mouse model of schistosomiasis. Elucidation of these aims should help to unravel the widely reported enigma of schistosome masking and the long-term survival of the parasite in the human bloodstream. By unmasking these parasites from their host-derived cloak, novel methods of controlling schistosomiasis will be revealed and efforts to develop a vaccine will be greatly accelerated.Read moreRead less