Humoral immune profiling of endemic schistosome-exposed individuals reveals epitopes associated with resistance to...

The development of an effective vaccine against schistosomiasis would represent a major advance toward controlling and eliminating this neglected tropical disease. Given the complexity of host-parasite interactions, we propose a multi-epitope vaccine strategy targeting immunogenic epitopes located at the host-parasite interface and associated with protective immune responses. In endemic areas, some individuals become resistant to reinfection (RR) after praziquantel (PZQ) treatment, while others remain susceptible to reinfection (SR).

We investigated the humoral immune responses of RR and SR individuals to identify epitopes associated with resistance, aiming to guide schistosomiasis vaccine design. Sera from RR and SR individuals living in an endemic area were collected 18 months after PZQ treatment and characterized for IgG1, IgG4, and IgE responses against soluble worm antigen preparation (SWAP) and tegument-enriched antigens (SmTEG). IgG and IgE recognition profiles were further evaluated using peptide microarrays containing 57 secreted or surface-exposed proteins from the parasite's alimentary tract, tegument and egg or cercarial secretions. Human IgG responses were compared with epitopes previously mapped in protected animal models, including mice immunized with the radiation-attenuated (RA) cercarial vaccine and rhesus macaques that self-cured.

RR individuals exhibited higher IgG1 responses against SWAP and SmTEG than SR individuals. Highly reactive epitopes were identified in Sm25 and ADP-ribosyl cyclase (tegument), MEG-12 and MEG-4.1 (esophageal gland), and LAMP (gastrodermis). While SR sera showed stronger reactivity to alimentary tract proteins, RR sera preferentially recognized tegument-associated targets. Notably, Sm25 and ADP-ribosyl cyclase contained three epitopes differentially recognized by the RR sera. Of the 17 human-prioritezed epitopes, 71% overlapped with those previously mapped in RA-immunized mice and 20% with those from self-curing rhesus macaques. The IgE response was weaker and more restricted, observed in only a few individuals.

These findings highlight key epitopes that warrant further investigation as components of multi-epitope vaccine constructs.