Characterization, cloning and immunogenicity of antigens released by transforming cercariae of Schistosoma mansoni

A schistosome infection is initiated when the parasite penetrates the skin of a susceptible host. Relatively large quantities of protein are released by transforming cercariae compared to later larval stages. This represents the first parasite material to which the host's immune system is exposed, y et little is known about the proteins which are released during the first f ew hours post-transformation. Mie have shown that antiserum raised against such molecules was capable of imparting protection against a schistosome ch allenge infection upon passive transfer to naive mice. By screening a cerca rial cDNA library with this serum, 38 positive clones were identified. Sequ ence analysis showed these to represent 8 different molecules which include d Schistosoma mansoni 21.7 kDa antigen, calcium-binding-protein and the vac cine candidate glutathione S-transferase (Sm28GST). In addition, 5 clones w ere isolated, 1 of which had significant homology to many cytochrome C prot eins, another with leukocyte elastase inhibitors and 3 which represented no vel molecules. Four clones were expressed in a prokaryotic high-level expre ssion vector, sera produced against each purified recombinant protein and u sed subsequently to probe Western blots and parasite sections. The leukocyt e elastase inhibitor homologue and 2 unknowns induced significant prolifera tion by lymph node cells recovered from mice Vaccinated with irradiated cer cariae. More strikingly, the 2 novel proteins stimulated very high levels o f interferon gamma (IFN gamma) secretion both by lymph node cells and those recovered by broncho-alveolar lavage from the lungs of vaccinated mice. Su ch results will be discussed in the context of vaccine development.