Authors

R C Oettle³; I W Chalmers¹; M Sacko²; S Wilson³;  ¹ Aberystwyth University - IBERS, UK;  ² Institut National de Recherche en Santé Publique, Mali;  ³ University of Cambridge, UK

Discussion

Schistosomiasis is a parasitic disease resulting from trematode worm infection. Schistosoma haematobium is the most prevalent causative organism, representing 112 million infections, the majority of which occur in sub-Saharan Africa. Severe morbidity results from immunopathogenic responses to eggs laid by adult worms. Sequelae include haematuria, squamous cell carcinoma of the bladder and female genital schistosomiasis, the latter being associated with an increased risk of human immunodeficiency virus (HIV) infection.

Significant progress has been made towards the control of schistosomiasis through mass annual preventative chemotherapy with praziquantel, however praziquantel does not prevent the frequent reinfection that results from ongoing exposure. Individuals therefore remain at risk of accumulating high worm burdens and tissue damage associated with eggs produced by mature female worms. There is therefore an ongoing need for research into alternative means of disease control.

Vaccines offer one conceivable solution since there is emerging evidence for slow acquisition of natural immunity to schistosomiasis. S. haematobium transmission is understood to be governed by immunity to reinfection (evidenced in all three species of schistosomes important to human health) and additionally, by a second means of immunity that modulates the number of eggs that mature female worms lay, known as worm fecundity. This immunity is also exhibited in closely-related schistosome infections of veterinary importance.

It has been demonstrated in a Malian cohort that the development of anti-fecundity immunity is associated with an IgG1 immune response. In the absence of a published protein microarray for S. haematobium, we used a conventional proteomic approach to explore the antigen recognition profile of IgG1 in this previously characterised cohort of individuals from Mali, known to have high levels of infection intensity. 

2D-Western blots were probed with sera from individuals from the cohort who demonstrate reduced egg to worm ratios, suggestive of reduced female worm fecundity. Proteins spots that were identified as differentially immunoreactive to the sera of cases compared to matched controls were subsequently sent for MS analysis. A review of associated literature and bioinformatic analysis was performed on those significant protein identifications.

Antigens that have previously been identified as having vaccine potential were identified, including 28kDa glutathione-S transferase, in addition to a number of proteins previously uncharacterised. The majority of proteins identified were cytosolic and a number had previously been identified as present in the tegument, extracellular vesicles or excretory/secretory products of schistosomes. Functional analysis indicated significant enrichment of proteins associated with energy metabolism, protein folding and reproductive processes. 

A subset of the identified proteins will subsequently be put through a high throughput bacterial expression system. The resulting recombinant proteins will be used in immunological assays across a full cohort of individuals in which there is variation in worm fecundity. This will provide further evidence to characterise anti-fecundity immunity at a population level.