Unbiased phage-display screening identifies Schistosoma mansoni vaccine candidates recognized by plasma from self-cured and challenge-resistant rhesus macaques (Macaca mulatta)

Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite's biological complexity. In this study, we utilized the innovative phage-display immunoprecipitation followed by sequencing (PhIP-Seq) technique to screen the rhesus macaque immune response during self-cure and challenge resistance phases, identifying new vaccine candidates. Our high-throughput S. mansoni synthetic DNA phage-display library displayed 99.6% of 119,747 58-mer encoded peptides, allowing a comprehensive coverage of the parasite's proteome. Library screening with rhesus macaques' antibodies identified significantly enriched epitopes of parasite extracellular proteins known to be expressed in the digestive tract, shifting towards intracellular proteins during parasite clearance. Immunization of mice with a selected set of PhIP-Seq enriched phage-displayed peptides from MEG proteins, cathepsins B, and asparaginyl endopeptidase significantly reduced worm burden. These findings enhance our understanding of parasite-host immune responses and provide promising prospects for developing an effective schistosomiasis vaccine.