Immunological characterization of a 47-amino acid segment of a candidate vaccine schistosome antigen

A 141-base pair (47-codon) segment of Schistosoma mansoni gene GP22 was previously isolated from a cDNA expression library using protective Fischer rat antiserum (F-2x). This gene encodes a 25-kD tegumental glycoprotein (Sm25), expressed in the juvenile and adult stages of the parasite life cycle, in addition to a subset of 18-22-kD precursors of Sm25 generated from three in-frame transcription initiation sites. These precursor products differ in length at the amino termini, but contain the same carboxy sequence, including the 47-amino acid segment. Rabbit antiserum to a recombinant protein incorporating the 47-aa segment, as well as monospecific antibodies to a peptide sequence (delta) within this segment, cross-react with several defined candidate vaccine antigens of both S. mansoni and S. japonicum, a related species. However, anti-delta antibodies fail to detect Sm25 in adult worm extracts. Additionally, F-2x does not contain antibodies with specificity for the delta sequence. Two alternative, but not mutually exclusive, models derived from these results propose the existence of multiple epitopes within this region, or postulate alternative conformations of a single epitope encoded by the delta sequence. A series of three immunization trials in laboratory rodents was performed using several recombinant proteins containing 2 or 4 copies of the 47-aa segment in tandem repeat the recombinant proteins. These recombinant proteins retained the characteristic of unique recognition by F-2x. While the injections elicited high antibody titers consisting of isotypes which correlate with protective functions, no resistance to challenge infection resulted, nor were any anti-fecundity effects observed. Immunization with the recombinant proteins neither augmented nor reduced the partial protection conferred by passive transfer of F-2x. If this segment does possess an immunological role in vivo, the conformational sensitivity of the uniquely recognized epitopes may require presentation within the context of the intact molecule.