Quantitative Proteomics of Enriched Esophageal and Gut Tissues from the Human Blood Fluke Schistosoma mansoni Pinpoints Secreted Proteins for Vaccine Development

Schistosomes are blood-dwelling helminth parasites that cause schistosomiasis, a debilitating disease
resulting in inflammation and, in extreme cases, multiple organ damage.
Major challenges to control the transmission persist, and the discovery
of protective antigens remains of critical importance for vaccine
development. Rhesus macaques can self-cure following schistosome infection,
generating antibodies that target proteins from the tegument, gut,
and esophagus, the last of which is the least investigated. We developed
a dissection technique that permitted increased sensitivity in a comparative
proteomics profiling of schistosome esophagus and gut. Proteome analysis
of the male schistosome esophagus identified 13 proteins encoded by
microexon genes (MEGs), 11 of which were uniquely located in the esophageal
glands. Based on this and transcriptome information, a QconCAT was
designed for the absolute quantification of selected targets. MEGs
12, 4.2, and 4.1 and venom allergen-like protein 7 were the most abundant,
spanning over 245 million to 6 million copies per cell, while aspartyl protease,
palmitoyl thioesterase, and galactosyl transferase were present at
<1 million copies. Antigenic variation by alternative splicing
of MEG proteins was confirmed together with a specialized machinery
for protein glycosylation/secretion in the esophagus. Moreover, some
gastrodermal secretions were highly enriched in the gut, while others
were more uniformly distributed throughout the parasite, potentially
indicating lysosomal activity. Collectively, our findings provide
a more rational, better-oriented selection of schistosome vaccine
candidates in the context of a proven model of protective immunity.