Phage display identification of vaccine candidates for schistosomiasis based on self-healing of rhesus monkeys (Macaca mulatta)

Abstract

Individuals of the genus Schistosoma are haemoparasites that cause schistosomiasis. The disease affects more than two hundred million people worldwide. In Brazil the schistosomiasis etiological agent is Schistosoma mansoni. Since the transcriptome publication of the species in 2003, little success has been achieved in the tests of vaccine candidates, and new methods for the recognition of new targets are necessary. One approach is the use of rhesus monkeys as the study model, which is able to spontaneously heal from Schistosoma infection. This project involves performing bioinformatic analyses, which are essential to explore the data that will be obtained by a novel phage display technology with synthetic oligonucleotides, which will do a screening of antibodies from infected and self-cured rhesus monkeys that are used for the first time as a model for this new technology. The synthetic oligonucleotides generated for the phage display library represent, with the same abundance in the library, all fragments of all parasite proteins having known sequences, allowing an unbiased selection of all antibodies from the rhesus monkeys that mediate self-healing. For the analyses of phage display data, large-scale sequencing will be performed in the phages captured by the serum samples of each of 11 infected monkeys collected at various times throughout the infection and cure. Bioinformatics analyses will be performed to obtain correlation and clustering of data on the abundance of epitopes recovered from captured phages in each monkey at each time. Probably those proteins targeted by the monkey's antibodies are critical for survival of the parasite. Thereby, we expect to identify several new parasite antigens that can be tested in future studies to generate a vaccine against schistosomiasis. (AU)