Abstract
SummaryLarvae of Schistosoma (schistosomula) are highly susceptible to host immune responses and are attractive prophylactic vaccine targets, although cellular immune responses against schistosomula antigens in endemic human populations are not well characterized. We collected blood and stool from 54 Schistosoma mansoni‐infected Ugandans, isolated peripheral blood mononuclear cells and stimulated them for 24 hours with schistosome adult worm and soluble egg antigens (AWA and SEA), along with schistosomula recombinant proteins rSmKK7, Lymphocyte Antigen 6 isoforms (rSmLy6A and rSmLy6B), tetraspanin isoforms (rSmTSP6 and rSmTSP7). Cytokines, chemokines and growth factors were measured in the culture supernatants using a multiplex luminex assay, and infection intensity was determined before and at 1 year after praziquantel (PZQ) treatment using the Kato‐Katz method. Cellular responses were grouped and the relationship between groups of correlated cellular responses and infection intensity before and after PZQ treatment was investigated. AWA and SEA induced mainly Th2 responses. In contrast, rSmLy6B, rSmTSP6 and rSmTSP7 induced Th1/pro‐inflammatory responses. While recombinant antigens rSmKK7 and rSmLy6A did not induce a Th1/pro‐inflammatory response, they had an association with pre‐treatment infection intensity after adjusting for age and sex. Testing more schistosomula antigens using this approach could provide immune‐epidemiology identifiers necessary for prioritizing next generation schistosomiasis vaccine candidates.
Highlights
There are currently 206.4 million people suffering from schistosomiasis worldwide[1] with the majority of infected individuals living in Africa
Antigens of the early schistosomula have been suggested as potential vaccine candidates.[21,35]
We first looked at immune responses to the crude parasite antigen preparations adult worm antigen (AWA) and soluble egg antigen (SEA)
Summary
There are currently 206.4 million people suffering from schistosomiasis worldwide[1] with the majority of infected individuals living in Africa. Schistosoma mansoni lymphocyte antigens, rSmLy6A and rSmLy6B ( known as SmCD59a and SmCD59b), are members of the three-finger protein domain (TFPD) superfamily They are homologous to the TFPD- containing human CD59, which protects human cells from complement fixation, rSmLy6A and rSmLy6B do not inhibit host complement fixation and as such their function remains unknown.[20] rSmLy6A and rSmLy6B are highly expressed by the schistosomula, and as probable GPI-anchored proteins on the schistosome tegument, they likely interact directly with host immune cells.[21] Schistosoma mansoni transmembrane proteins, tetraspanins rSmTSP6 and rSmTSP7, to other tetraspanin family members, are thought to be involved in cell membrane biology.[19,22] As all of the proteins described above are at the interface between the parasite and the host immune system, and may be novel vaccine antigens, we assessed the cellular responses to these antigens in individuals residing in an S. mansoni endemic area
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