Previous observations, which showed that treatment of mice with hydrocortisone acetate around the time of their infection with Schistosoma mansoni reduced the mature worm burden, have been confirmed. The number of eggs produced by the surviving worms during early patency was also significantly reduced. Cyclophosphamide and another steroid immunosuppressant, betamethasone, also caused a reduction in fecundity of S. mansoni when given at the time of infection, as did T-cell deprivation of the mice by adult thymectomy and injection of anti-thymocyte serum 1 month before infection. There was no effect of these three treatments on worm numbers. In contrast, injection of mice with anti-thymocyte serum at the time of infection marginally increased the size of the mature worm burden. The deleterious effects of hydrocortisone acetate on S. mansoni worm numbers and fecundity were only apparent if the steroid was given within 1 week of infection. Indomethacin, a compound which inhibits tissue inflammatory reactions by inhibiting prostaglandin synthesis, and which therefore mimics one of the actions of corticosteroids, had no effect on S. mansoni worm maturation and fecundity.

SUMMARYMice infected with 25 to 35 unsexed Schistosoma mansoni cercariae became resistant to homologous challenge by 8 weeks, and the degree of resistance that was acquired correlated with the size of the worm burden and the tissue egg burden. Mice given 100 male or 100 female cercariae alone failed to become resistant even after 30–40 weeks of infection. When a super-infection of 100 male or 100–300 female cercariae was given to mice with 25 unsexed cercariae, the degree of resistance that was acquired was generally lower than in mice given 25 unsexed cercariae alone. In the super-infected mice there was no correlation between the size of the worm burden (mainly unpaired male or female worms) and the degree of acquired resistance. In mice super-infected with male worms there was an inverse correlation between the number of male worms and the number of eggs deposited in the liver and intestine by each mature worm pair. A positive correlation was, however, still found between the degree of acquired resistance and total tissue egg counts in mice super-infected with single sex cercariae. Mice injected intraperitoneally or subcutaneously with intact S. mansoni eggs failed to become resistant to S. mansoni challenge. Transfer of lymphoid cells or serum, separately or together, from heavily infected and demonstrably resistant donor mice to naive normal or T-cell deprived recipients failed to render the recipients resistant to S. mansoni challenge. The results indicate that resistance to re-infection in mice with recently patent S. mansoni infections is dependent on the number of S. mansoni eggs entrapped in the tissues, and that excessive numbers of unpaired S. mansoni male or female worms can inhibit the fecundity of established worm pairs. The apparent acquired resistance to S. mansoni that has been observed in this model system may be largely a consequence of non-specific factors interfering with normal patterns of challenge worm migration and maturation.

C57BL/6 and Balb/c mice were immunized with ultraviolet-irradiated cercariae of Egyptian strains of Schistosoma mansoni and S. haematobium, challenged with nonirradiated cercariae of the homologous or heterologous species, and assayed for protection against challenge infection by comparing the adult worm burdens of immunized and non-immunized mice. Homologous protection (per cent reduction in worm recovery) ranged from 56% to 69% for S. mansoni and 88% to 99% for S. haematobium. Significant heterologous protection was consistently induced against S. haematobium by immunization with S. mansoni, but not against S. mansoni by immunization with S. haematobium. These results are discussed in relation to those of previous studies and in terms of implications for vaccine development.

We have shown previously that baboons (Papio anubis) develop high levels (greater than 80%) of protection against challenge infection following immunization with Schistosoma haematobium cercariae irradiated with 20 krad. In the present study baboons were immunized with schistosomula irradiated with either 20 krad or 60 krad, with variations in the timing and number of larvae comprising each vaccination. Baboons immunized 2 or 3 times with schistosomula irradiated with 20 krad were significantly more protected (85-90%) against challenge infection than baboons similarly immunized with larvae receiving 60 krad (56-50% protection). Baboons immunized with schistosomula irradiated with 20 krad were better protected against challenge infection at 8 weeks after immunization than at 28 weeks after immunization. Protection was manifest by a reduction in worm numbers, tissue and excreta egg counts, gross pathology and, to a lesser extent, by stability of body weight and haematological indices following challenge. Enzyme-linked immunosorbent assay (ELISA) results of selected baboon sera showed few differences related to irradiation dose alone, but titres were higher in baboons receiving booster immunizations, and there was a significant correlation between titres immediately preceding challenge and the degree of resistance. Examination of responses to individual schistosomular surface antigens by immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed no correlation between the pattern of antigens recognized and resistance status. As with the ELISA assay, an anamnestic response was detected after vaccination, while the amount of antibody present declined markedly with increasing time after individual immunizations.