Evaluation of the Schistosoma mansoni Y-box-binding protein (SMYB1) potential as a vaccine candidate against schistosomiasis

Abstract

Schistosomiasis is a neglected tropical disease, and after malaria, is the second most important tropical disease in public health. A vaccine that reduces parasitemia is desirable to achieve mass treatment with a low cost. Although potential antigens have been identified and tested in clinical trials, no effective vaccine against schistosomiasis is available. Y-box-binding proteins (YBPs) regulate gene expression and participate in a variety of cellular processes, including transcriptional and translational regulation, DNA repair, cellular proliferation, drug resistance, and stress responses. The Schistosoma mansoni ortholog of the human YB-1, SMYB1, is expressed in all stages of the parasite life cycle. Although SMYB1 binds to DNA or RNA oligonucleotides, immunohistochemistry assays demonstrated that it is primarily localized in the cytoplasm of parasite cells. In addition, SMYB1 interacts with a protein involved in mRNA processing, suggesting that SMYB1 functions in the turnover, transport, and/or stabilization of RNA molecules during post-transcriptional gene regulation. Here we report the potential of SMYB1 as a vaccine candidate. We demonstrate that recombinant SMYB1 stimulates the production of high levels of specific IgG1 antibodies in a mouse model. The observed levels of specific IgG1 and IgG2a antibodies indicate an actual protection against cercariae challenge. Animals immunized with rSMYB1 exhibited a 26% reduction in adult worm burden and a 28% reduction in eggs retained in the liver. Although proteins from the worm tegument are considered optimal targets for vaccine development, this study demonstrates that unexposed cytoplasmic proteins can reduce the load of intestinal worms and the number of eggs retained in the liver.

rSJYB1 inhibits collagen type I protein expression in hepatic stellate cells via down‐regulating activity of collagen α1 (I) promoter

“…SMYB1 has been verified the ability to bind DNA and RNA like other Y‐box proteins and may act in the process of RNA metabolism . Furthermore, mice immunized with the recombinant SMYB1 (rSMYB1) were detected the high levels of specific anti‐rSMYB1 antibodies in their sera . SJYB1 reported in our study shares 83.33% identity in its nucleotide sequence and 94.47% in its protein sequence with SMYB1 (data not shown).…”

“…Recombinant SJYB1 inhibited the expression of collagen type I, but not α‐SMA in LX‐2 cells, suggesting that rSJYB1 specifically regulates synthesis of collagen type I rather than HSC activation. Unexpectedly, another study on mice infected with S mansoni has revealed that infected mice immunized with rSMYB1 exhibited reductions in the number of adult worm and eggs/granuloma retained in the liver, but no significant decrease was detected in the area of fibrosis . It is possible that the roles of YB1 from schistosomes in vitro are not entirely consistent with that in vivo.…”

Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?

“…Firstly, in 2014, publications from three Brasilian groups reported protection against schistosome challenge after vaccination of mice using what are unquestionably intracellular proteins. The four proteins were Syntenin [ 1 ], Dynein light chains DLC12 and DLC13 [ 2 ], and Y box protein [ 3 ]. Secondly, we undertook a quantitative shotgun proteomic analysis of the ubiquitous antigen preparation SWAP, the soluble cytosolic extract of adult worms [ 4 ].…”

Immunization with adultSchistosoma mansonitegument, treated with sub-curative praziquantel, partially protects mice against the infection

“…There is still a lack of agreement on the type of immune response that needs to be induced by a vaccine candidate to achieve a satisfactorily high degree of protection against schistosome infection (Dias et al , 2014). The cellular Th1 profile characterized by an increase in IFN-γ has been shown to be more effective in preventing experimental schistosomiasis, although a strong Th2 or a mixed Th1/Th2 response was associated with reducing the worm burden (Rofatto et al , 2013).…”