Anyiam, Abimbola (2012) Evolutionary processes affecting molecular diversity and antigentic variation in the vaccine target protein tetraspanin 23 of the human parisite 'Schistosoma mansoni'. (MSc(R) thesis), Kingston University, .

Abstract

Schistosomiasis is caused by parasitic blood flukes of the genus Schistosoma with an estimated 240 million people infected in tropical and sub-tropical regions of the world. Due to the decrease in efficiency of praziquantel in mass drug administration programmes, the elucidation of a viable vaccine target has been paramount. Tetraspanins (TSPs) are a superfamily of proteins that are located in the cell membrane of multiple organisms. Research on TSPs in 'Schistosoma japonicum' and 'Schistosoma mansoni' has identified tetraspanin 23 (TSP23) as a prime candidate as it is a tegumental protein expressed on the surface of the parasite. It has an extracellular loop that is directly presented to the host's immune system with the vast majority of antibodies raised by the host targeted against it. However, there appears to be little immune memory towards these parasites upon re-infection, and recent studies on S. 'japonicum' show that TSP23 vaccines only exhibit a partial protection against the fluke. Molecular and bioinformatic analysis of TSP23 from different populations of S. 'mansoni' have shown the extracellular loop 2 to be hypervariable arising from allelic isoforms of the protein. Subsequently, variations in protein structure and antigenicity have been detected. Multiple TSP23 genotypes and protein variants are present amongst a sub-population. The multiple genotypes and protein variants are a product of increased recombination in response to positive selection. High frequency of recombination is arising within the antibody binding sites due to the selection pressures placed by continuous immunoglobulin interactions with the protein. Consequently, this mechanism ultimately produces a highly diverse protein. The characteristics described above could be problematic for the use of TSP23 as vaccine candidate, as it is hypervariable and genetically diverse. Notably, other TSPs do not share the same characteristics as TSP23. Whilst it is evident that TSP23 is undergoing adaptive evolution, other TSPs may not be. As such other TSPs should be investigated as opposed to TSP23, as they offer more promising prospects.

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