Abstract
Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, divergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis. Bacterially expressed recombinant peptides corresponding to regions excluding trans-membrane domains of the selected vaccine targets were used in blinded vaccine trials in CBA mice using alum-CpG as adjuvant. Vaccine trials using the recombinant insoluble Sm-LAMP protein showed 16–25% significant reduction in total worm burden. Faecal egg count reduction was 52% and 60% in two trials, respectively, with similar results for the solubly expressed protein. Liver egg burden was reduced significantly (20% and 38%) with an insoluble recombinant Sm-LAMP in two trials, but not with the soluble recombinant form. Parasite fecundity was not affected by either Sm-LAMP protein preparations in the trials. It is concluded that Sm-LAMP may provide limited protection towards S. mansoni infections but could be used in combination with other vaccine candidates, to provide more comprehensive protection.
Highlights
Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni
We focus on two antigens, a schistosome lysosome-associated membrane glycoprotein (Sm-LAMP) and Niemann Pick type C2 protein (Sm-NPC2)
We previously reported that 393 genes were up-regulated in the gastrodermis of adult female worms of S. mansoni compared with whole female parasite tissue[27]
Summary
Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. We selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. Two S. mansoni tetraspanins (TSP 1 and TSP2), which are tegument-associated molecules originally uncovered by signal sequence trap methods and tegument proteomic surveys, have shown promising vaccine efficacies[13,14] Another outer membrane protein of the tegument of S. mansoni, Sm29, is a promising vaccine target against which putative resistant individuals in endemic settings have developed a strong IgG1 and IgG3 isotype response[15,16]. Molecules expressed at the surface of the schistosome gastrodermis may provide good targets as vaccine candidates due to their location and importance in nutritional support of the parasite
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