T cell mediated immunity to Schistosoma japonicum infection and vaccination

Abstract

Schistosomiasis is a chronic parasitic disease and considered by the World Health Organization (WHO) to be second to malaria as the most devastating parasitic disease in terms of socioeconomic importance and public health impact. Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Similarly, study on the effect of a particular vaccine candidate on the immune response is important as it can provide insight as to how to modulate the immune response in order to develop a more efficacious vaccine. Therefore, the aims of this project were to evaluate the T cell immune response to S. japonicum infection and following vaccination.nCBA mice were percutaneously exposed to cercariae of S. japonicum and the immune response at different time points was determined. There was a relatively robust Th1 immune response to schistosomal adult worm antigen preparation (SWAP) at the early phase of infection. However, a Th2 immune response was dominant at weeks 6 post-infection, a time point when the highest IgG response, determined by ELISA, against both SWAP and, especially, SEA was generated. The regulatory immune response was most pronounced at the early phase of the immune response followed by a rapid decline at week 6-post infection.nOur laboratory at QIMR Berghofer has targeted the ligand binding domain (LD1) of the insulin receptor (SjIR) and triose-phosphate isomerase (rSjTPI) as putative vaccine candidates against schistosomiasis japonica, both having generated encouraging levels of protection in mice. Consequently an antigen mix comprising the two vaccine proteins (rSjTPI-LD1) was prepared, and the immune response generated to it analysed in CBA mice randomly grouped into two groups. The first group was subcutaneously injected with rSjTPI-LD1 vaccine formulated with Montanide ISA 720VG (day 0) and boosted twice (on day 15 and day 30). The second group of control mice were injected with PBS and Montanide ISA 720 VG using the same immunization protocol. Two weeks after the final booster vaccination, the two groups of mice were challenged with 34 S. japonicum cercariae and the immune response at different time points was determined using IgG-ELISA and flow cytometry. There were partial but significant reductions in worm and liver egg burdens in the vaccinated animals compared with the adjuvant control group indicating the vaccine had generated partial protection in the mice. In addition, significantly higher levels of anti-rSjTPI and anti-rSjLD1 IgG antibodies were induced in the vaccinated group with the peak level occurring at week 4 post-challenge. Moreover, rSjTPI-LD1 induced both Th1 and Th2 immune responses at the early phase of the immune response mediated by CD8+ and gd T cells; a Th17-mediated response induced at a later stage. rSjTPI-LD1 significantly induced a regulatory T cell (Treg) immune response in vaccinated mice.nOverall, depletion of Tregs may improve the efficacy of rSjTP-ILD1 and further study on gd T cells with regard to vaccine-induced immunity against schistosomiasis may pave the way to the development of a more efficacious vaccine.nn