Screening the Schistosoma mansoni transcriptome for genes differentially expressed in the schistosomulum stage in search for vaccine candidates

Abstract

Schistosomiasis affects more than 200 million people worldwide; another 600 million are at risk of infection. The schistosomulum stage is believed to be the target of protective immunity in the attenuated cercaria vaccine model. In an attempt to identify genes up-regulated in the schistosomulum stage in relation to cercaria, we explored the Schistosoma mansoni transcriptome by looking at the relative frequency of reads in EST libraries from both stages. The 400 genes potentially up-regulated in schistosomula were analyzed as to their Gene Ontology categorization, and we have focused on those encoding-predicted proteins with no similarity to proteins of other organisms, assuming they could be parasite-specific proteins important for survival in the host. Up-regulation in schistosomulum relative to cercaria was validated with real-time reverse transcription polymerase chain reaction (RT-PCR) for five out of nine selected genes (56%). We tested their protective potential in mice through immunization with DNA vaccines followed by a parasite challenge. Worm burden reductions of 16-17% were observed for one of them, indicating its protective potential. Our results demonstrate the value and caveats of using stage-associated frequency of ESTs as an indication of differential expression coupled to DNA vaccine screening in the identification of novel proteins to be further investigated as potential vaccine candidates.

Schistosoma mansoni Venom Allergen Like Proteins Present Differential Allergic Responses in a Murine Model of Airway Inflammation

“…(A) Upper panel: the developmental stages of the life cycle of schistosomes; (B) SmVALs (mRNA or protein) expressed in these developmental stages. The arrow (↑) indicates up-regulation in a particular stage by Real-time RT-PCR [5], [42] or Microarray data [43], [44], [45]; (•) Identification of the correspondent SmVAL protein or (• j ) SjVAL by proteomics data [6], [7], [8], [11], [12], [13], [14]. M and F – male and female adult worms, * previously reported on the Schistosoma transcriptome analysis [4], (panel (A) was extracted and modified from [4]).…”

Stage and tissue expression patterns of Schistosoma mansoni venom allergen-like proteins SmVAL 4, 13, 16 and 24

“…The targets were secreted proteins going from cercariae penetration to the beginning of blood-feeding by adult worms. The criteria were to choose members from group 1 (SmVAL4 and 24) and group 2 (SmVAL 13 and 16) with high expression levels in parasite stages that could interact with the definitive host [16, 17, 19]. We also provide additional information on the SmVAL6 transcript previously localized by Rofatto et al [18].…”

Discovery of novel Schistosoma japonicum antigens using a targeted protein microarray approach

“…Sj-L6L-1 has significant homology to a S. mansoni antigen that was briefly investigated in a DNA vaccine study [31] and recently designated Sm-CD59.2 [32]. Finally calponin-like protein has a predicted size of 27 kDa and has some homology with a 38 kDa  S. japonicum calponin homologue (accession #AAD11976; 63% identity) previously investigated [33].…”

“…Previously, two of the members of this family were identified in the adult S. mansoni worm tegument using proteomics [47]. Farias et al [31] analysing the S. mansoni transcriptome for genes up-regulated from the cercariae to the schistosomula, identified SmCD59.2 (which they refer to as ‘dif 5’) and performed a limited DNA vaccine trial which resulted in a slight (but non-significant) reduction (22%) in worm burden.…”