Blueprint for schistosomiasis vaccine development.

A number of different schistosome antigens are capable of partially protecting experimental animals from challenge infection. More than 100 such antigens have been identified, about 15% of which are strongly protective and deemed promising though they do not reach the level close to sterile immunity seen after vaccination with irradiated cercariae. Studies of human correlate reactions, i.e. serological reactions and cytokine responses to schistosomiasis antigens, in individuals living in areas endemic for schistosomiasis have shown associations between certain antigen-specific immune responses and lack of re-infection over time. This approach was applied in Brazil and Egypt where it was possible to epidemiologically follow cohorts of individuals in endemic areas for extended periods of time correlating infection status with immune responses against a panel of well-researched, highly purified vaccine candidates. The immune correlates found were unique to each antigen and could be either positive or negative, i.e. associated with resistance or with susceptibility to re-infection. However, few antigens were clear-cut in this respect, i.e. the majority of them induced ambiguous responses. For example, a single antigen might have a significant positive correlation when antigen-driven interferon (INF)-gamma production is measured but also show a significant negative correlation with respect to the IgG1 titre induced. These observations suggest that there are desirable, antigen-specific immune responses that would be valuable in a vaccine but they also indicate that there are responses that must be avoided. The insights gained should be useful not only for antigen selection but also for vaccine formulation prior to Phase I/II trials in humans. It would be of great value if similar independent, long-term human correlate studies could also be undertaken in areas endemic for Schistosoma japonicum.

In vitro cellular and humoral responses to Schistosoma mansoni vaccine candidate antigens.

Few studies comparing schistosomiasis vaccine candidate antigens between laboratories have been carried out and published. Generally, only the investigators who discovered the molecules have evaluated them in either experimental animal models or in human correlate studies. In an attempt to identify responses against specific antigens and investigate their association with resistance versus susceptibility to re-infection, we studied the serological reactions and the cytokine responses stimulated by a panel of 10 candidate vaccine molecules in 225 long-term residents of an area endemic for Schistosoma mansoni in Egypt. The panel consisted of four recombinant antigens (Sm62-Irv5, Sm37-G3PDH, Sm28-GST and Sm14-FABP), one full-length native protein (Sm97-paramyosin), two synthetic peptides (MAP3 and MAP4) and three unpublished antigens (PR52-filamin, PL45-phosphoglycerate kinase, PN18-cyclophilin). Two different study designs, one based on retrospective and the other on prospective parasitological data were applied in the evaluation of the immune responses. Using historical data collected over the previous 5 years, correlations between frequency of re-infection and antigen-specific immune responses were investigated. In the prospective arm of the study, the subjects were followed over time after treatment with praziquantel with periodic immunological tests and stool examinations. Thus, highly specific humoral and cellular immune reactions in response to the 10 antigens described above could be correlated, both prospectively and retrospectively, with detailed epidemiological data covering a 66-month period. The immune response profiles produced were unique to each antigen but no clear "winner" or "winners" were identified. However, markers for both resistance and susceptibility to re-infection were identified for each molecule indicating which types of responses to aim for in vaccination and which ones to avoid. The insights gained from this approach should be useful for antigen selection and ultimately for vaccine formulation prior to Phase I/II trials in humans.