Altruism in nature: an investigation of transmission-blocking immunity against malaria
- Research Opportunity
- Project Status
- Medicine and Radiology
- Royal Melbourne Hospital
|A/Prof Siddhartha Mahantyemail@example.com|
|Prof Stephen Rogersonfirstname.lastname@example.org||+61 3 8344 3259||Personal web page|
The malaria parasite Plasmodium falciparum (Pf) has a complex lifecycle with asexual and sexual stages in two hosts, humans and mosquitoes. Transmission of malaria parasites from humans to the mosquito vector is a complicated phenomenon that successfully overcomes immune defences in both hosts. Immune responses directed towards to sexual (transmittable) stages in humans of are capable of inhibiting parasite growth in mosquitoes, thus interrupting transmission of malaria without benefiting the host, a concept referred to as altruistic immunity. Antibodies directed against sexual stages of Pf are thought to directly mediate growth inhibition of sexual stages. The extent of antibody-mediated immunity against Pf gametocytes, the sexual stage in humans, and the functional properties of antibodies that underlie growth inhibition are not well understood.
The goal of this project is to identify malaria-infected individuals who have antibodies to gametocytes and gametocyte-derived antigens of Pf and to determine the functional properties of anti-gametocyte antibodies that confer transmission-blocking properties.
- Hypothesis: Pf-infected individuals have antibodies against gametocyte stages of the parasite and that functional properties of these antibodies determine their ability to block transmission
- Study design: Sera from malaria-infected individuals from Pf endemic regions will be screened for antibodies against gametocytes and gametocyte-derived antigens. Antibodies from highly reactive sera will be characterized for biochemical and functional properties (receptor binding, opsonisation and parasiticidal activity). The functional characteristics will be correlated with transmission blocking activity to identify the most closely correlated properties. Methodology used: ELISA, flow cytometry, immunofluorescence, statistical methods for quantitative analysis of data
- Envisaged role of trainee: Development of ELISA assays to screen infected sera for antibodies to gametocytes and gametocyte antigens; functional characterization of reactive antibodies.
- Significance: A better understanding of the mechanisms of transmission blocking immunity will facilitate the development of vaccines aimed blocking transmission – an “altruistic” vaccine
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