Schistosomiasis is a highly prevalent disease which affects over 200 million people throughout the developing world. A vaccine that is capable of inducing partial protection from infection could considerably reduce schistosome-associated morbidity in the tropics.
In this study, work has been carried out to develop a vaccine based on S. mansoni cercarial elastase, one of the proteases which enables the entry of the parasite into the mammalian host by digesting components of the skin and connective tissue. This protease was found to be located within the pre-acetabular glands of the cercariae. It appeared to be poorly immunogenic when administered with other cercarial antigens and when encountered during natural infections. The proteases of three different schistosome species, S. mansoni, S. haematobium and S. margrebowiei, were shown to be immunologically cross-reactive. This indicated that a vaccine based on the protease of one species might be effective against infection from several different schistosome species.
Recombinant S. mansoni-elastase was produced as an S. japonicum-glutathione-Stransferase fusion protein. This protein was tested for its ability to protect against a challenge S. mansoni infection in several different mouse immunization experiments. All mice immunized with the fusion protein produced antibody that reacted with native elastase in Western blots. The immunized mice were consistently found to have reduced group mean worm burdens compared with control groups. However, the extent of the reductions varied from 16 to 39 percent between the experiments.
A sixteen amino acid peptide suspected to be a B-cell epitope was selected from
exon-2 of elastase using the computer program Predict7. This peptide was
chemically synthesized and conjugated to thyroglobulin. All mice immunized with this construct were found to produce antibody which reacted with the peptide conjugated to ovalbumin yet only a proportion of these mice produced antibody capable of binding to the native elastase. In five out of seven experiments carried out, the mice immunized with this B-cell epitope peptide conjugate were found to have a lower group mean worm burden than the challenge control mice. When the results from all the experiments were combined the immunized mice were found to have on average seven percent less worms than the control mice and the difference between the immunized and the control mice was found to be statistically significant. Some of the experiments indicated that there was an association between the ability of the
immunized mice to produce antibody that was reactive with native elastase and
protection. This however was not apparent in other experiments.
A possible T-cell epitope was selected from the amino acid sequence of elastase using two different computer programs. This peptide was combined with the B-cell epitope peptide in several different constructs. The incorporation of this peptide into the vaccine did not improve its effectiveness.