Zhao-Song Zhang

Association between IgE antibody against soluble egg antigen and resistance to reinfection with Schistosoma japonicum.

There is evidence that immunoglobulin (Ig) E antibody may be a critical component of protective immunity against Schistosoma mansoni and S. haematobium reinfection. In the present study, 555 individuals aged 3-67 years infected with S.japonicum received praziquantel treatment before the transmission season commenced; 45 d later, blood samples from 265 individuals who had no S. japonicum egg in their stool were examined by enzyme-linked immunosorbent assay for specific isotypic antibodies. Single, non-conditional logistic regression analysis showed that exposure intensity, age, soluble egg antigen (SEA)-IgE, SEA-IgM and soluble adult worm antigen-IgG4 were relevant to reinfection; multiple, non-conditional logistic regression analysis showed that exposure intensity was still a significant factor for reinfection while the SEA-IgE antibody level was associated with resistance to reinfection with S. japonicum, with a protective index of 2.00. It is suggested that this population in an area endemic for schistosomiasis japonica exhibits acquired immunity.

Th1-type epitopes-based cocktail PDDV attenuates hepatic fibrosis in C57BL/6 mice with chronic Schistosoma japonicum infection.

Schistosomiasis is one of the worlds major public health problems in terms of morbidity and mortality, which is characterized by a marked egg-induced CD4(+) T-cell programmed granulomatous inflammation and cumulative fibrosis. Here PDDV (peptide-DNA dual vaccine), a widely used non-viral gene delivery system, was applied. The cocktail PDDV, based on four Th1-type epitope peptides identified from Schistosoma japonicum vaccine candidates and CpG ODN1826, could induce dominant Th1-type response in C57BL/6J mice (P<0.05). The histopathological staging and collagen assessment for fibrosis showed that the cocktail PDDV presented an obvious down-regulation effect on hepatic fibrosis caused by chronic S. japonicum infection (P<0.05), and IFN-gamma, IL-4 and IL-13 mRNAs in liver detected by RT-PCR also showed that the cocktail PDDV represented the ability to up-regulate Th1-type responses, which paralleled with a decrease expression of alpha-SMA (P<0.05) and the up-regulated MMP9/TIMP1 balance (P<0.05) when compared to the control groups. Therefore, it is indicated that the cocktail PDDV can significantly attenuate hepatic fibrosis, in parallel with the decreased HSCs activation and the up-regulated MMP9/TIMP1 balance in favor of matrix degradation, which may be partially dependent on the increased Th1 response to restore the Th1/Th2 balance.

T cell epitope-based peptide-DNA dual vaccine induces protective immunity against Schistosoma japonicum infection in C57BL/6J mice.

Schistosomiasis is a major public health problem that primarily affects developing countries. Although schistosomicidal drugs exist, the development of an efficacious vaccine would potentially be the most powerful means of controlling this disease. Previous studies have shown that vaccination with selected protective epitopes successfully induced partial protection and/or reduced female fecundity in animal models. Thus, we investigated whether the T cell epitope P5 from the host-interactive tegument of Schistosoma japonicum 22.6 (S. japonicum) could act as a protective epitope. The protective potential of P5 in a vaccine against S. japonicum was determined by using a T cell epitope based peptide-DNA dual vaccine (PDDV). In our experiments, the vaccine construct (P5-18K-PDDV) contains the peptide of the T cell epitope (P5) and plasmid DNA, encoding P5 and adjuvant GM-CSF. We show that P5-18K-PDDV induced both cell-mediated and humoral immune responses in vivo and achieved partial protection against S. japonicum infection in C57BL/6J mice. Histopathological studies reveal that P5-18K-PDDV immunized mice had substantially reduced liver pathology compared to the control groups. Together, these results suggest that P5 could be used as a vaccine immunogen for both worm killing and disease prevention against S. japonicum.

Down-regulation of specific antigen-driven cytokine production in a population with endemic Schistosoma japonicum infection.

Schistosome antigen‐driven cytokine responses and antischistosome antibody levels of residents of a Schistosoma japonicum endemic island in Poyang Lake, Jiangxi Province were studied before and 45 days after treatment with praziquantel. IL‐4, IL‐5, IL‐10 and INF‐γ were all detected in the supernatants of whole‐blood cultures after stimulation with schistosome soluble egg antigen (SEA) and soluble worm antigen preparation (SWAP). The percentages of subjects producing detectable amounts of each cytokine assayed were higher in the group who were negative by stool examination at the start of the study than in those who were initially stool positive. After praziquantel treatment the percentages of subjects producing both type I and type II cytokines increased. This suggests that the production of both types of cytokine was down‐regulated in the presence of live, egg‐laying S. japonicum adult worms but that this was reversible by treatment. In contrast, the antibody studies showed higher levels of SWAP and SEA‐specific antibodies (IgE, total IgG, IgG4, IgM) in subjects who were originally stool‐positive than in those who were stool‐negative. After treatment specific IgE responses were elevated, but total IgG and IgG4 anti‐SEA and IgM anti‐SWAP antibody levels all fell significantly.

IFN-γ is associated with risk ofSchistosoma japonicuminfection in China: Immunity toSchistosoma japonicum

Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum‐endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool‐positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty‐five days later the 93 subjects who presented for follow‐up were all stool‐negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL‐4, IL‐5 and IFN‐γ production in whole‐blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re‐screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA‐induced IFN‐γ production were associated with reduced risk of infection.