Integrative reverse vaccinology approach for identification of a vaccine antigen candidate with immunoprotective and anti-fibrotic potential against Schistosoma japonicum-associated liver fibrosis

Abstract

Schistosoma japonicum-associated liver fibrosis (SSLF) is a major cause of morbidity in Schistosomiasis, yet no licensed vaccines or specific therapies exist to prevent or treat this complication. Current vaccine development has focused mainly on infection prevention, with limited attention to pathology-driven outcomes such as fibrosis. To address this gap, we developed an in-silico pipeline integrating host single-cell transcriptomic analysis, parasite antigen screening, and structure-based modeling. Single-cell RNA-seq of liver tissues from SSLF and controls identified three fibrosis-related hub proteins: FYN, BCL2, and AKT3. In parallel, parasite antigens curated from public databases were evaluated for immunogenicity and safety using reverse vaccinology principles. Among these, DRE2_SCHJA, an Anamorsin homolog involved in Fe-S cluster assembly, was prioritized as the top candidate. Docking analysis predicted the strongest interaction between DRE2_SCHJA and FYN ({Delta}G = -14.9 kcal/mol), linking the antigen to a central regulator of fibrosis. Unlike Saracatinib, which inhibits FYN at the ATP-binding pocket, DRE2_SCHJA bound to the SH2 domain through both canonical and non-canonical contacts, indicating a different regulatory mechanism. Taken together, these findings suggest DRE2_SCHJA as a potential vaccine candidate with both protective and anti-fibrotic potential against SSLF. While experimental validation is required, this study supports the early identification of SSLF vaccine candidates in a rapid and cost-effective manner and provides a framework applicable to other neglected tropical diseases. Athor summarySchistosoma japonicum (S. japonicum) is a parasitic disease that remains a major health problem in parts of Asia, especially in China. One of its most harmful consequences is liver fibrosis, which causes long-term illness and reduces quality of life. Currently, there are no drugs or vaccines that specifically prevent or treat this condition. In this study, we used a fast and low-cost computer-based method to search for vaccine targets against liver fibrosis caused by S. japonicum. We identified a parasite protein that could serve as a vaccine target, with the potential to prevent fibrosis from developing and to slow its progression. If future studies confirm its role, such a vaccine could greatly improve the long-term health of people living with schistosomiasis and inspire new strategies for vaccine development in other neglected tropical diseases.