Characterisation of the naturally-acquired antibody response to the surface of Plasmodium falciparum infected erythrocytes.

Mackintosh, Claire Louise (2006). Characterisation of the naturally-acquired antibody response to the surface of Plasmodium falciparum infected erythrocytes. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000fb2b

Abstract

The surface of P. falciparum-infected erythrocytes is modified by the insertion of immunogenic parasite-encoded proteins; the most extensively studied family is Plasmodium falciparum erythrocyte membrane protein 1, (PfEMP1). PfEMP1 undergoes clonal antigenic variation and is responsible for mediating cytoadherence of infected erythrocytes within the microvasculature, characteristics underpinning the virulence associated with Plasmodium falciparum infection. Protection against disease following exposure to a parasite displaying a particular variant of PfEMP1 is associated with agglutinating antibodies against that variant, antibodies associated with protection. However, the role of cross-reactive responses to heterologous isolates in protection from subsequent disease remains poorly understood. The target and epitope specificity of both the variant specific protective response and any cross-reactive antibody response is unknown.

Individuals from two areas with differing transmission characteristics were screened at the end of a low transmission season for recognition of a panel of laboratory and clinical isolates. Using in particular an isolate selected to express one specific variant of PfEMP1, A4 PfEMP1, on the surface of the host erythrocyte, the relationship between the presence of asymptomatic parasite carriage and cross-reactive antibody responses was established. Subsequently the domain and interdomain regions of A4 PfBMP1 were cloned and expressed as recombinant proteins and used to screen the same individuals in an attempt to identify the targets for these measured responses. This study demonstrated differences in antibody acquisition between domains, individuals and areas. In a longitudinal study, the interaction between having detectable parasites and the ability to recognise the surface of erythrocytes infected with four different parasite isolates led to the identification of a susceptible group of children responsible for the burden of clinical malaria in this area.