Identification of CAA as highly specific and sensitive antibody target for acute schistosomiasis diagnostics

BackgroundThe WHO 2030 roadmap for schistosomiasis calls for development of highly sensitive and specific diagnostic tools to continue and sustain progress towards elimination. Serological assays are excellent for sensitive detection of primary schistosome infections and for schistosomiasis surveillance in near- and post-elimination settings. To develop accurate assay formats, it is necessary to identify defined antibody targets with low cross-reactivity and potential for standardized production. Here we focus on defined schistosome glycan antigens. MethodsTarget identification was performed by assessing antibody responses in well characterized cross-sectional and cohort sample sets (n=366 individuals) on tailor-made antigen microarrays. IgM and IgG binding to candidate diagnostic targets was measured for serum/plasma samples from: controlled human schistosome infection model (CSI), schistosome infected travellers, soil-transmitted helminth infected and non-infected individuals. FindingsWe found that antibodies to circulating anodic antigen (CAA) identify schistosome infection with high sensitivity (IgM[≥]100%, IgG[≥]97%) and specificity (IgM[≥]93%, IgG[≥]97%) in the test samples. Infection dose affected timing of anti-CAA antibody isotype switch. Furthermore, we demonstrate the presence of shared and non-specific glycan epitopes in crude schistosome cercarial and egg antigen preparations. Many non-specific glycan epitopes contained in crude antigen mixes are responsible for a large proportion of false schistosomiasis positives in standard serological assays. InterpretationCAA is target for development of highly sensitive and specific tools for schistosomiasis serology with use cases for travellers and surveillance in near and post-elimination settings as well as emerging transmission zones. FundingGlobal Health Innovative Technology Fund (GHIT), HIC-Vac, Leiden University Medical Center (LUMC)