Assessing the mechanisms of self-cure in rhesus macaques infected with Schistosoma mansoni as a new basis for a vaccine

Abstract

Schistosomes are flatworm flukes widely distributed around the world that cause schistosomiasis. They infect over two hundred million people and are, thus, framed as a global public health concern. In 2003, we published the first large-scale transcriptome dataset of Schistosoma mansoni, the etiologic agent in Brazil. This dataset has provided a number of potential targets that have been tested extensively in the literature as vaccine candidates. Unfortunately, very limited progress has been achieved with the candidates tested so far, and new approaches are necessary to screen for possible novel candidates. One such approach involves the rhesus macaque study model, which is capable of spontaneously self-cure from Schistosoma infection. The present proposal aims at identifying the yet-to-be-discovered molecular mechanisms involved in the self-cure of rhesus macaques infected and challenged with S. mansoni. Specifically, we will seek which antibodies the rhesus macaques generate that are responsible for the immune reaction capable of eliminating parasites, and we will then identify the targets of these antibodies. In order to achieve this we propose to use, for the first time in this model, the phage display technology, which will provide an unbiased screening of all the rhesus macaques antibodies that may mediate the self cure and that can be directed against any known S. mansoni protein. We expect to identify many new antigen candidates as vaccine targets that can be tested in future studies for the development of a vaccine against schistosomiasis. (AU)