Multi-epitope schistosome vaccine candidates tested for protective immunogenicity in mice

The major challenge in the development of anti-schistosome vaccines is to u se defined antigens to stimulate an appropriate immune response that leads to resistance. Several promising candidate vaccine antigens including the g lycolytic enzyme triosephosphate isomerase (SmTPI), a 28 kDa glutathione-S- transferase (Sm28), the myofibrilar protein paramyosin (Sm97), an integral membrane protein (Sm23) and calpain (Smcalpain) have been characterised and their primary sequences derived for Schistosoma mansoni. Furthermore, sequ ences are available For synthetic peptides mimicking epitopes on these mole cules capable of inducing schistosmne-specific T- and B-cell responses. The se schistosome vaccine candidates have generally been tested with varying d egrees of success as single components, with only one report of the use of a multivalent antigen or multi-epitope approach. We describe the assembly o f multiple defined and different epitopes of S. mansoni into a variety of s ingle covalent structures; these included a DNA vaccine encoding different epitopes in tandem, the polyprotein itself that is encoded by this DNA acid branched synthetic peptide epitope-based polymers in which the individual epitopes are pendant from an inert backbone. Each of the vaccine constructs examined, with the exception of the DNA vaccine, generated antibodies that were capable of binding to a tandem sequence of the epitopes. Although the se results were encouraging, none of the constructs protected animals from subsequent challenge infection, indicating that the immune responses elicit ed were inadequate or inappropriate for parasite killing in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved.