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  • Given that CE plays an essential role in schistosome invasio

    2020-07-01

    Given that CE plays an essential role in schistosome invasion, its immunoreactivity and protective potential is of significant interest. The native form of SmCE was found to be poorly immunogenic in immunized mice. An earlier study found that sera from S. mansoni patients have shown the presence of IgG and IgM anti-CE UNC 3230 sale reflecting exposure, but not necessary an active infection (Ramzy et al., 1997). Furthermore, it was reported that mice immunized with S. mansoni cercarial transformation fluid generating antibody against 27 kDa serine protease are partly protected against infection (Darani et al., 1997; Darani and Doenhoff, 2009). Another investigation showed that S. mansoni, S. haematobium, S. japonicum and Trichobilharzia ocellata infection induces antibodies against cercarial secretions, but not against the cercarial elastases of these parasite species, implying that although CE is present in cercarial secretions, it is not apparently immunogenic during natural infection (Bahgat et al., 2001). The poor immunogenicity of cercarial serine protease is likely due to the host primitive defence mechanism mounted against the invading parasite, or the parasite’s ability to cleave host IgG and IgE molecules to overcome the antibody response (Aslam et al., 2008; Darani and Doenhoff, 2009). An investigation reported that rats immunized with recombinant 28 kDa S. mansoni elastase showed a high level of effector antibodies IGg2a, and that native elastase in mouse skin upon cercaria invading was immunolocalized by rabbit antisera against recombinant elastase (Pierrot et al., 1996). These findings imply that elastase could be a target of immune attack by the host. However, little is known of whether animals immunized with recombinant elastase will exhibit immunity to parasite infection. A more recent study showed that a recombinant SmCE fused to recombinant S. japonicum glutathione S-transferase resulted in smaller mean worm burden and lower tissue egg counts in immunized mice, but with no indication of statistic significance (El-Fahma et al. 2017). In short, to date most of investigations have been with focus on S. mansoni cercarial proteases. Clarifying the immunogenic property of SjCE is one of our aims in the present study. We have previously shown that recombinant SjCE-2b could be recognized by infected rabbit serum, and the native protease by anti-recombinant SjCE-2b sera in infected mouse skin (Huang et al., 2007; ). Building on these findings, we present here a statistically significant reduction in both adult worms and liver egg counts in S. japonicum infected mice immunized with rSjCE-2b, indicating this protease exhibited a certain level of immunoprotective effect upon cercaria invasion. It is noted that the reduction rates were statistically significant but biologically not striking, however, the purpose of this in vivo immunoassay was to testify whether the SjCE-2b be able to induce immunogenic response against parasite infection, rather than to identify a vaccine candidate. On the other hand, the immunoprotective effect may involve complicated molecular and immunological mechanisms, in which CE may not be a sole element. Other factors impacting on the effectiveness of the mice immunization could include the antigen amount given and the scheduling of dosages. It is reasoned that to optimize this immune-response using a variety of adjuvants, antigen amounts, and vaccination protocols, and to demonstrate more direct proteolytic evidence by skin test will be the future research goal. Nevertheless, our positive result apparently differs from what was found of SmCE with poor immunogenicity. It is thus important to further understand the notable difference in this regard between the two species. A total of nine SmCE isoforms have been identified thus far in S. mansoni, among them SmCE-2b was speculated to be more evolutionarily ancient than other isoforms and may have a different function in the skin invasion process and beyond in the parasite life cycle (Ingram et al., 2012). Whether there are other isoforms of S. japonicum CE and the associated hypothesis is yet to be verified.