Abstract
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 is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is 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 and show decreased 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.
Highlights
The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide
Eggs appeared in the faeces at Wk6 and linear regression of eggs per gram of faeces (EPG) on time between Wk6 and Wk10 gave a y zero value at 5.8 weeks (40 days) for apparent female maturation
We stratified our subjects into Fast (Rh2, 3, 4 and 9) and Slow responder groups (Rh5, 6, 8 and 11) based on an unsupervised principal components analysis of data from all 15 acquired parameters, and on their self-cure rate
Summary
The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. 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 postchallenge plasma. To inform and accelerate the pace of vaccine development, the rhesus macaque model has recently been revisited, to establish the parameters of a primary infection with S. mansoni[18] and S. japonicum[19], using small numbers of animals. A total of 15 different parameters are followed over 62 weeks, and these data provide a solid foundation on which to base future work aimed at identifying both the antigens mediating self-cure and the immunological mechanism(s) that allow the rhesus macaque to exhibit solid immunity after eliminating its worm population
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