Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge

The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni was cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrated that protection was strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development as well as showing altered expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine. Stranded tagged cDNA libraries were prepared by BGI using the Strand-Specific Transcriptome Library Construction Protocol (DNBSEQ, SOP-SS-115) and quantification and quality were performed on a 2100 Bioanalyzer (Agilent). Libraries were pooled and sequenced (300 cycles, paired-end sequencing) on a MGISEQ-2000 instrument.