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Anti-glycosylphosphatidylinositol antibodies as new tool in malaria research

English title Anti-glycosylphosphatidylinositol antibodies as new tool in malaria research
Applicant Pluschke Gerd
Number 116337
Funding scheme Project funding (Div. I-III)
Research institution Swiss Tropical and Public Health Institute
Institution of higher education University of Basel - BS
Main discipline Experimental Microbiology
Start/End 01.04.2007 - 31.03.2009
Approved amount 225'143.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Medical Microbiology

Keywords (3)

plasmodium falciparum malaria; GPI-anchored proteins; immune protection

Lay Summary (English)

Lead
Lay summary
Glycosylphosphatidylinositols (GPIs) anchor proteins in the membrane of virtually all eukaryotic cells from vertebrates to protozoa and constitute up to 90% of protein glycosylation in protozoan parasites. Also the surface of extra-cellular forms of the human malaria parasite Plasmodium falciparum is thus coated by GPI-anchored proteins, but genomic and proteomic studies suggest that only a minority of these proteins have been identified so far. Parasite surface proteins are crucially involved in host-parasite interactions and several of the known GPI-anchored proteins of P. falciparum are regarded as key candidate antigens for a multi-valent malaria subunit vaccine. We have raised monoclonal antibodies (mAbs) against synthetic GPI and will use these to identify and study the GPI-anchored proteome of P. falciparum and other parasite species. Immunological and biochemical methods in combination with mass spectrometry for protein identification will be used. Based on criteria, such as stage-specific expression patterns, predicted protein-protein interactions and the presence of protein domains of particular interest, a set of newly identified GPI-anchored proteins will be selected for heterologous expression and the production of specific serological reagents. These will be used to study expression patterns at the protein level, protein processing, sub-cellular localization and biological roles. Furthermore we will evaluate the potentially protective role of anti-GPI antibody responses. Among the bioactive molecules produced by the parasites, GPI has emerged as a central toxin that induces the expression of many host genes implicated in malaria pathogenesis. In particular the induction of pro-inflammatory cytokines by GPIs appears to be an important element in the development of severe malaria. While a GPI-based vaccine has delayed malaria mortality in a rodent malaria model, it has been challenging to establish a direct correlation between anti-GPI antibody levels and immune protection in humans. We will therefore analyse anti-parasite activities of anti-GPI mAbs in vitro and in vivo. Our analysis is expected contribute to the understanding of host-parasite interactions in malaria. New vaccine candidate antigens representing suitable components of a multivalent malaria subunit vaccine may be identified and characterised.
Direct link to Lay Summary Last update: 21.02.2013

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