Human IgG1 responses to surface localised Schistosoma mansoni Ly6 family members drop following praziquantel treatment

Background the heptalaminate-covered,syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term,intravascular residence in definitive hosts. investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. recent studies have revealed a number of novel tegumental surface proteins including three (smcd59a,smcd59b and sm29) containing upar/ly6 domains (renamed smly6a smly6b and smly6d in this study). while vaccination with smly6a (smcd59a) and smly6d (sm29) induces protective immunity in experimental models,human immuno-globulin responses to representative smly6 family members have yet to be thoroughly explored. methodology/principal findings using a psi-blast-based search,we present a comprehensive reanalysis of the schistosoma mansoni ly6 family (smly6a-k). our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate sm29 (renamed smly6d) is a unique double upar/ly6 domain-containing representative. presence of canonical cysteine residues,signal peptides and gpi-anchor sites strongly suggest that all smly6 proteins are cell surface-bound. to provide evidence that smly6 members are immunogenic in human populations,we report igg1 (as well as igg4 and ige) responses against two surface-bound representatives (smly6a and smly6b) within a cohort of s. mansoni-infected ugandan males before and after praziquantel treatment. while pre-treatment igg1 prevalence for smly6a and smly6b differs amongst the studied population (7.4% and 25.3%of the cohort,respectively),these values are both higher than igg1 prevalence (2.7%) for a sub-surface tegumental antigen,smtal1. further,post-treatment igg1 levels against surface-associated smly6a and smly6b significantly drop (p = 0.020 and p < 0.001,respectively) when compared to rising igg1 levels against sub-surface smtal1. conclusions/significance collectively,these results expand the number of smly6 proteins found within s. mansoni and specifically demonstrate that surface-associated smly6a and smly6b elicit immunological responses during infection in endemic communities. © 2015 chalmers et al.