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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in immunology and vaccination

Neutralization of malaria glycosylphosphatidylinositol in vitro by serum IgG from malaria exposed individuals.

LSHTM investigators:
Brian de Souza, Kevin Couper, Patrick Corran, Lucy Okell, Tom Doherty, Colin Sutherland & Eleanor Riley.
External collaborators:
Channe Gowda (Pennsylvania State University, USA); Geoff Pasvol (Imperial College London, UK).
Funding body:
Wellcome Trust.

Parasite-derived glycosylphosphatidylinositol (GPI) is believed to be a major inducer of the pathways leading to pathology and morbidity during malaria infection and has been termed a malaria “toxin”.

The generation of neutralising anti-GPI (“anti-toxic”) antibodies has, therefore, been hypothesised to be an important step in the acquisition of anti-disease immunity to malaria; however to date the GPI-neutralising capacity of antibodies induced during natural malaria infection has not been evaluated. We have developed an in vitro macrophage-based assay to assess the neutralising capacity of malarial GPI-specific IgG. We demonstrate that IgG from Plasmodium falciparum-exposed individuals can significantly inhibit GPI-induced activation of macrophages in vitro, as shown by reduced TNF production and attenuation of CD40 expression. The GPI neutralising capacity of individual IgG samples was directly correlated with anti-GPI antibody titre.  IgG from malaria-exposed individuals also neutralised the macrophage activating effects of P. falciparum schizont extract (PfSE) but there was only a poor correlation between PfSE neutralising activity and anti-GPI antibody titre, suggesting that PfSE contains other macrophage activating moieties in addition to GPI.  In conclusion, we have established an in vitro assay to test the “toxin” neutralising activity of anti-malarial antibodies and have shown that anti-GPI antibodies from malaria immune individuals are able to neutralise GPI- induced macrophage activation; however the clinical relevance of anti-GPI antibodies remains to be proven given that malarial schizonts contain other pro-inflammatory moieties in addition to GPI.