Vorschau

PDF, Englisch - Hauptdokument Download (11MB) | Nutzungsbedingungen

Abstract

Plasmodium falciparum is a unicellular parasite that throughout its complex lifecycle infects Anopheles mosquitos and humans. The parasite stages injected into the human by the mosquito are called sporozoites and can be neutralized by antibodies generated by the human immune system. The present study investigates the humoral immune response, i.e. the antibody response, to the major antigen on the sporozoite surface, circumsporozoite protein (CSP). A recently published study describes high-affine anti-CSP antibodies, which are generated upon repeated controlled human malaria infection of European donors, who were never exposed to the parasite before. The present work on the one hand describes the molecular characteristics that determine the binding of such antibodies. On the other hand, it investigates whether African donors from an endemic malaria region exhibited similar antibodies. In the repertoire of the European donors, several groups of antibodies were identified that share highly similar amino acid sequences and binding behaviours. It is shown that these antibodies can only bind to the antigen if very specific sequence characteristics are conserved. This probably restricts the number of potential B cell precursors that can lead to the generation of such antibodies. The most important result of this study is the observation that antibodies binding the repetitive region of CSP directly interact with each other. The antibodies even show signs of anti-idiotope affinity maturation directed against the antigen binding site of neighbouring antibodies. Surprisingly in none of the three probed African donors antibodies with measurable anti-CSP reactivity could be found. The present work suggests that this is due to the low frequency of B cell precursors, but also due to the specific binding mode that is induced by the repetitive CSP structure.