Improving the development of a vaccine candidate against schistosomiasis by analyzing the humoral and cellular immune responses from rhesus macaques self-cured against Schistosoma mansoni

Abstract

Schistosomiasis is a very debilitating disease, spread across three continents and infecting more than 200 million people. Administration of praziquantel to infected individuals is the basis of current schistosomiasis therapy; however, cure rates of less than 50 % have been recorded and drug tolerance has been already reported, reinforcing the need for new and more effective approaches in reducing morbidity and/or in achieving disease eradication, such as the development of a vaccine. Over the last four decades, there have been several attempts to develop a vaccine for schistosomiasis by testing many different vaccine candidates, which were selected based on their known location on the parasite and on putative function of the candidate proteins, but the results have been disappointing and there is no vaccine available against the disease to date. Vaccination is pointed as the most interesting strategy to prevent schistosomiasis, making large-scale programs possible at lower costs. Vaccines can be developed by the study of resistance models to parasitic diseases, as already achieved to Haemonchus contortus. In schistosomiasis, we have recently described the mechanisms of rhesus macaques self-cure and resistance to a primary infection and challenge against S. mansoni, and we have identified new peptide vaccine candidates against schistosomiasis. In this project, we propose to deepen the understanding of the immune response that enables rhesus macaques to self-cure from schistosomiasis, as a tool to facilitate the development of a vaccine against the disease. To do this, we will identify S. mansoni glycans recognized by rhesus macaques' antibodies using glycan microarrays, and characterize and analyze immune cell subpopulations from rhesus macaques infected and challenged with S. mansoni using CyTOF and RNA-Seq. With this information, we expect to improve a vaccine formulation using novel vaccine candidate peptides already identified by our group, which will potentially achieve WHO goals for a satisfactory protection level in further preclinical and clinical protection assays.