Protective Immune Responses Generated in a Murine Model Following Immunization with Recombinant Schistosoma japonicum Insulin Receptor

Abstract

There is a pressing need to develop vaccines for schistosomiasis given the current heavy dependency on praziquantel as the only available drug for treatment. We previously showed the ligand domain of the Schistosoma japonicum insulin receptor 1 and 2 (rSjLD1 and 2) fusion proteins conferred solid protection in mice against challenge infection with S. japonicum. To improve vaccine efficacy, we compared the immunogenicity and protective efficacy of rSjLD1 on its own and in combination with S. japonicum triose-phosphate isomerase (SjTPI), formulated with either of two adjuvants (QuilA and montanide ISA 720VG) in murine vaccine trials against S. japonicum challenge. The level of protection was higher in mice vaccinated only with rSjLD1 formulated with either adjuvant; rSjTPI or the rSjTPI-rSjLD1 combination resulted in a lower level of protection. Mirroring our previous results, there were significant reductions in the number of female worms (30⁻44%), faecal eggs (61⁻68%), liver eggs (44⁻56%), intestinal eggs (46⁻48%) and mature intestinal eggs (58⁻63%) in the rSjLD1-vaccinated mice compared with the adjuvant only groups. At 6-weeks post-cercarial challenge, a significantly increased production of interferon gamma (IFNγ) in rSjLD1-stimulated splenic CD4⁺ T cells was observed in the rSjLD1-vaccinated mice suggesting a Th1-type response is associated with the generated level of protective efficacy.