Antibody Responses to Recombinant Oligopeptides of PfEMP1 Isolated From Children Infected With Plasmodium falciparum

Tuju, James Owindi (2013). Antibody Responses to Recombinant Oligopeptides of PfEMP1 Isolated From Children Infected With Plasmodium falciparum. PhD thesis The Open University.



Individuals living in malaria endemic areas acquire immunity against clinical disease through repeated encounters with the Plasmodium falciparum parasite during their childhood. As a result, the majority of severe cases of malaria are restricted to younger children. Naturally acquired immunity is thought to be partly mediated by antibodies directed at parasite derived antigens on the surface of red blood cells infected with mature forms of P. falciparum called variant surface antigens (VSA). Of these, P. falciparum erythrocyte membrane protein 1 is well characterized and associated with pathology and immune evasion. Sera obtained from young children living in endemic areas show limited recognition of PfEMP1 unlike immune adult sera that exhibit recognition of a wide range of PfEMP1. It is not yet clear whether this wide recognition of PfEMP1 by adult immune sera is exclusively a product of variant specific response accumulated over many exposures or whether it includes a cross-reactive response that recognizes a diverse set of antigens.

Here, I have used the recombinant DBLα-tag region of PfEMP1 generated from parasites isolated from children infected with malaria to show that individuals develop a strong variant-specific response to their infecting isolate, accompanied by partly cross-reactive response. Based on antigenic and genetic similarities between different DBLα-tag variants, I identified potential epitope regions in this study that may account for the cross reactive responses. However, these appear to be conformational and predominantly lie towards the N-terminal end. Once verified, such regions may form good candidates for inclusion in a multi-epitope vaccine construct that affords broad protection against malaria.

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