Identification of antigenic epitopes of the parasite Schistosoma mansoni targeted by the immune response of self-cured and reinfected-resistant rhesus macaques (Macaca mulatta) using a Phage display library containing synthetic DNA sequences

Schistosomiasis, caused by parasites of the genus Schistosoma, is a Neglected Tropical Disease (NTD) widely spread throughout the world. Currently, the only available therapeutic and prophylactic approach is Praziquantel; however, its effectiveness is limited, and resistance to this medication has been observed. Additionally, efforts to develop a vaccine against schistosomiasis have been frustrated over the past decades. The present research aimed to identify new effective vaccine targets against the disease. To achieve this, the study is based on two main strategies. First, the process of self-cure and resistance to challenge in rhesus macaques infected with S. mansoni was explored to understand the immune response involved in these phenomena. The second strategy evaluated antigens recognized by antibodies generated in rhesus macaques during selfcure and after challenge through the construction and screening of a phage display display library containing 119,747 synthetic DNA sequences in the phage inserts, which encode 58-mer peptides covering all 58-amino acid segments of all ~12,000 known parasite proteins. The 58-mer antigens significantly recognized by rhesus macaques antibodies were evaluated in relation to the infection and challenge periods in which they were detected, and in relation to the subcellular localization, and expression organs of their respective proteins. The 58-mer peptides belonging to seven different proteins expressed in the parasites digestive tract were identified as promising vaccine targets and tested in a pilot vaccine test. The pilot immunization strategy provided partial protection in mice. The information obtained from the two strategies allowed the understanding of the immune response of rhesus macaques to S. mansoni and the identification of candidate vaccine targets. (AU)