Host immune network-guided reverse vaccinology approach for prioritizing candidate antigens in Schistosoma japonicum-associated liver fibrosis.

Schistosoma japonicum-associated liver fibrosis (SSLF) remains a major cause of long-term morbidity in schistosomiasis, even in post-control or low-transmission settings. While most vaccine development efforts have focused on reducing parasite burden, few approaches have incorporated host pathology related to liver fibrosis. This study developed an in silico strategy that combined host single-cell analysis with reverse vaccinology to guide the exploratory screening of parasite antigens with potential relevance to SSLF. Single-cell transcriptomics of fibrotic and control human liver tissues was used to identify immune-related molecular networks and host proteins associated with fibrosis-related pathology in the available dataset. In parallel, antigens were screened by functional annotation and established reverse-vaccinology criteria. Candidate antigens were further assessed by docking against selected host proteins. Docking of a known FYN inhibitor was included as a structural reference to interpret the strongest predicted antigen-host interaction. Single-cell analyses identified FYN, BCL2, and AKT3 as key nodes in fibrosis-associated immune networks. Among screened parasite antigens, DRE2_SCHJA, an Anamorsin homolog involved in iron-sulfur cluster assembly, emerged as a computational candidate for further validation. Docking predicted that DRE2_SCHJA may bind in an SH2-associated region of FYN, whereas the Saracatinib-FYN model was centered on the ATP-binding pocket of the kinase domain. This difference may suggest a distinct predicted binding mode rather than Saracatinib-like kinase inhibition. Overall, the vaccine-screening profile and predicted FYN-associated interaction may provide a computational rationale for further experimental evaluation of DRE2_SCHJA as a candidate antigen in the immune-fibrotic context of SSLF.