Effect of combined praziquantel and recombinant glutathione S-transferase on resistance to reinfection in murine Schistosomiasis mansoni

This study was undertaken to evaluate the effect of recombinant Schistosoma mansoni-26 Glutathione S-transferase (rSm 26 GST) or soluble egg antigen ( SEA) alone and in addition to praziquantel (PZQ) on the state of resistance to S, mansoni reinfection. The associated changes in the immune responses were evaluated. The experimental group of mice were injected intravenously before S. mansoni infection (80 cercariae/mouse) either with rSm26 GST (1 m ug x 4) or SEA (10 mug x 4) in addition to PZQ (2 x 500 mg/kg) administered 6 weeks post-infection. Seven control groups were used, three of them were the infected (80 cercariae/mouse), the challenged (240 cercariae/mouse) an d the infected challenged controls (80+240 cercariae/mouse). The rest of th e four groups were the treated controls receiving: the GST-Lyzate, rSmGST, SEA and PZQ in the same doses and at the same timings. Challenge infection was conducted for all the groups 8 weeks post-infection. Animals were sacri ficed 3 weeks post-challenge. After sacrifice animals were perfused and per centage resistance to reinfection was calculated. Immune responses were ass essed by the measurement of hepatic granuloma diameter, intralesional T-cel l phenotypes and serum immunoglobulin isotypes. The highest percentage of r esistance to reinfection was observed in rGST-treated group while the lowes t percentage of resistance was detected in PZQ-treated group. Whereas in mi ce receiving combined rGST or SEA and PZQ, percentage resistance to reinfec tion was significantly higher than that in PZQ treated mice. The remarkable reduction in granuloma diameter in rGST-treated group with or without PZQ was associated with decrease in the intralesional L3T4+ and increase in Lyt (2)(+) T-cell phenotypes. However, no special relationship was observed bet ween the percentage of resistance and the changes in granuloma diameter or intralesional T-cell phenotypes. The increase in percentage resistance to r einfection was found accompanied by increased anti SWAP IgE. Combined rGST and PZQ provided the complementary goals of improved state of resistance to reinfection 'which was compromized after cure with PZQ' and the maximal re duction in granuloma diameter. (C) 2000 Published by Elsevier Science Ltd o n behalf of International Society for Immunopharmacology. All rights reserv ed.