c Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted Nglycans with terminal mannose residues, Gal␤1-4GlcNAc (LacNAc) and Gal␤1-4(Fuc␣1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAc␤1-4(GlcNAc␤1) n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAc␤1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage-and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection. Schistosomiasis is one of the neglected tropical diseases with the highest impacts on human health. Over 230 million people are infected worldwide, and over 500 million are at risk of infection (1-3). Infection leads to chronic disease characterized by pronounced immunological reactions against eggs deposited into host tissues by the adult schistosome worms, which eventually lead to fibrosis and organ failure (2). Although effective treatment is available, reinfection occurs rapidly and immunity develops only slowly, stressing the need for a prophylactic vaccine as part of a sustainable control strategy (4-6).Schistosomes have a complex life cycle with different life stages that interact with the human host and that each play a role in immunology, immunopathology, and maintenance of infection. Schistosoma infection occurs after direct contact with water containing the larval form of the parasite (cercariae). Cercariae penetrate the host skin and transform into schistosomula, which enter the vasculature and mature while migrating via the lungs to the portal ve...