Updated project metadata. Schistosomes are blood-dwelling helminth parasites causing a debilitating disease in the tropics. Major challenges to control persist and vaccines would provide an additional tool, but their development has been problematic. During the self-cure response of Rhesus macaques, antibodies target proteins from the tegument, gut and esophagus, the last of which is the least investigated. We developed a dissection technique that permitted comparative proteomics on the schistosome esophagus and gut. A shotgun analysis applied to male heads identified 13 MEG proteins, eleven of which were uniquely located in the esophageal glands. Antigenic variation by alternative splicing of MEG proteoforms was confirmed together with a specialised machinery for protein glycosylation in the esophagus. Moreover some gastrodermal secretions were highly enriched in the gut, while others were more uniformly distributed, potentially as markers of lysosomal activity. Collectively, our findings provide a more rational, better-oriented selection of schistosome vaccine candidates in the context of a proven model of protective immunity.