CANDIDATE VACCINE ANTIGENS THAT STIMULATE THE CELLULAR IMMUNE-RESPONSE OF MICE VACCINATED WITH IRRADIATED CERCARIAE OF SCHISTOSOMA-MANSONI

Vaccination with radiation-attenuated cercariae confers the highest le vels of resistance to challenge infection in experimental schistosomia sis and requires Ag-specific T cells. Therefore, this study aimed to i dentify specific Ag that stimulate the cellular immune response of mic e vaccinated with irradiated cercariae of Schistosoma mansoni. Four ex perimental groups representing different levels of resistance in the v accine model (C57BL/6J versus CBA/J mice vaccinated with 15- or 50-kra d irradiated cercariae) were compared for in vitro lymphocyte prolifer ation and lymphokine production. Adult worm extracts fractionated by i soelectric focusing were used as Ag. Lymphocyte proliferation of all g roups was limited to three consecutive isoelectric fractions (pH 4.6-6 .3). Interestingly, the antibody response of these mice was directed t o Ag in the same isoelectric fractions, three of which had previously been identified as paramyosin, heat shock protein 70, and the integral membrane protein Sm23. These Ag as well as two 28 kDa proteins, trios ephosphate isomerase and glutathione S-transferase, i n purified nativ e or recombinant form or as a synthetic peptide, stimulated lymphocyte proliferation. Lymphocytes of vaccinated C57BL/6J mice generally show ed higher levels of proliferation than did CBA/J mice. Interestingly, cells of once-vaccinated mice responded better than did cells of mice vaccinated three times. Lymphokine assays demonstrated that IL-2 and I L-4 was generally reduced after multiple vaccinations and varied quali tatively as well as quantitatively between mouse strains. This study s ubstantiates that the five Ag, paramyosin, heat shock protein 70, trio sephosphate isomerase, glutathione S-transferase, and the integral mem brane protein Sm23, are important candidates for a defined anti-schist osomal vaccine.