Mechanisms of transmission-blocking immunity against malaria
- Research Opportunity
- Project Status
- Medicine and Radiology
- Royal Melbourne Hospital
|Assoc Prof Siddhartha Mahantyemail@example.com|
|Prof Stephen Rogerson|
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 complex process that requires the parasite to overcomes immune defences in both hosts. Antibodies directed against sexual stages of Pf can directly inhibit growth of sexual stages (gametocytes). The extent of antibody-mediated immunity against Pf gametocytes, the sexual stage in humans, and the functional properties of antibodies that can block transmission, are not well understood.
The goal of this project is to characterize immune mechanisms underlying transmission blocking immunity mediated by antibodies to sexual stage parasites in human malaria. To investigate these mechanisms, we will identify malaria-infected individuals who have antibodies to gametocytes and gametocyte-derived antigens of Pf and determine the biophysical and functional properties of anti-gametocyte antibodies that confer transmission-blocking properties.
A better understanding of the mechanisms of transmission blocking immunity will facilitate the development of vaccines aimed blocking transmission – an “altruistic” vaccine.
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 biophysical and functional properties (characterizing properties such as IgG isotypes, receptor binding, opsonisation, phagocytic efficiency, NK cell activation, cytokine stimulation and parasiticidal activity). The functional characteristics will be correlated with transmission blocking activity to identify the most closely correlated properties.
Methodology employed: ELISA, flow cytometry, immunofluorescence, antibody subclass analysis, opsonisation, bead phagocytosis assays, NK activation, statistical methods for quantitative analysis of data
Faculty Research Themes
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