The host-parasite relationship of Schistosoma haematobium in CBA mice.

The host-parasite relationships of two geographical isolates of Schistosoma haematobium in CBA mice are described and compared to previous reports on this parasite in other experimental hosts and in man. The mean percentage establishment of worms in mice was 17% and was not affected by the age or sex of the host. Adult worm burdens remained constant over 20 weeks, but were reduced after 18 months of infection. Male and female worms reached mean maximum lengths of 4.78 and 5.9 mm respectively. Egg laying commenced 9.5 weeks after infection and eggs accumulated in the tissues throughout the period of infection. A large increase in the rate of egg accumulation occurred coincidental with the appearance of eggs in the bladder of some mice. Faecal eggs were first observed in some mice at 12.5 weeks and most mice excreted a few eggs by 17 weeks p.i. (post-infection). Eggs were not found in the urine of infected mice. Excreted eggs and eggs isolated from the livers of infected mice hatched, but the resulting miracidia were unable to infect appropriate snail hosts. The development of hepatic granulomas and egg-induced pathology in the bladder of mice is described.

Specific cross-protection between Schistosoma bovis and S. haematobium induced by highly irradiated infections in mice.

Significant levels of resistance against Schistosoma haematobium challenge were developed by mice exposed to highly irradiated (20 krad) cercariae of the homologous species (46-53%) or of the closely related species, S. bovis (34-56%) but not of S. mansoni (-6-28%). This ability to cross-protect reflects the phylogenetic relationships between these species; S. mansoni and S. bovis, as well as S. mansoni and S. haematobium, failed to cross-protect. The cross-protection demonstrated between S. bovis and S. haematobium in mice was non-reciprocal.

Cross-protection between species of the Schistosoma haematobium group induced by vaccination with irradiated parasites.

Mice vaccinated with irradiated cercariae of Schistosoma haematobium, S. bovis and S. margrebowiei showed good levels of resistance (38-62%) against an homologous challenge, and varying degrees of resistance (19-46%), against challenges with closely related species. No protection against S. mansoni was induced by vaccination with any of these species. This restricted cross-protection reflects the close phylogenetic relationship between species of the S. haematobium group and indicates that immunologically important epitopes are conserved within this species complex.

Immune attrition of adult schistosomes.

Mouse infection models are described that demonstrate reduction in the rate of egg production in Schistosoma haematobium worms 6-10 weeks after the onset of oviposition and loss of Schistosoma bovis worms around 10 weeks after infection. Neither phenomenon has been shown in Schistosoma mansoni- or Schistosoma japonicum-infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by transference of the ability to reduce a S. bovis worm burden in immuno-compromised hosts with immune serum. Vaccination with irradiation-attenuated parasites of S. haematobium was also shown to have consequences for the adults of challenge infections of either S. haematobium or of S. bovis, but not of S. mansoni. Thus, prior vaccination resulted in an abrogation of the reduced egg production by S. haematobium and S. bovis worms and also of the adult worm elimination that occurred in non-vaccinated S. bovis-infected mice. These models are being used to define the targets and mechanisms involved in the attrition of adult worms of schistosomes with terminal spined eggs.

Schistosoma bovis as an immunological analogue of S. haematobium.

The host-parasite relationships of Schistosoma bovis and S. haematobium have been compared in normal and T-cell-deprived mice, and have been found to contrast with that of S. mansoni. Deprived mice infected with either of the former two schistosome species survived as long as, or longer than, comparably infected immunologically intact controls, and hepatocytes of infected deprived mice were not damaged in the absence of granuloma formation. S. mansoni-infected deprived mice, however, die earlier than intact controls, and suffer extensive hepatocellular abnormalities. A high degree of cross-reactivity between S. bovis, S. haematobium and S. mansoni antibodies and antigens was noted in immunoprecipitation but a greater degree of homology between S. haematobium and S. bovis egg antigens was demonstrated by enzyme immunoassay (ELISA). S. haematobium and S. bovis thus resemble each other more closely than either resembles S. mansoni, and in view of the apparent antigenic similarities between S. haematobium and S. bovis and the relatively greater ease with which the S. bovis life-cycle can be maintained in the laboratory, the animal parasite may be useful in providing material for further immunological studies of the human infection.

Schistosoma mansoni egg antigens: preparation of rabbit antisera with monospecific immunoprecipitating activity, and their use in antigen characterization.

A simple method for producing monospecific rabbit antisera, applied originally to the constituents of human serum (Goudie et al. 1966), has been adapted for use with Schistosoma mansoni egg antigens. Replicate isolated immunoprecipitin arcs resulting from the immunoelectrophoretic reaction between an egg antigen and a polyspecific antiserum were excised, washed extensively to remove non-precipitated contaminants, homogenized, and emulsified with complete Freund's adjuvant. Rabbits were given weekly subcutaneous injections of the emulsion in multiple sites, and a monospecific precipitating antibody against the respective immunizing antigen generally resulted within 6 weeks of the commencement of immunization. Antisera raised in this manner against S. mansoni egg antigens omega 1, alpha 1 and kappa 5 have been used to characterize the antigen with respect to their stage- and species-specificity. After immunoabsorption to remove background activity, the sera could be used to detect unequivocally the respective antigens in crude egg homogenate that had been subjected to SDS-PAGE and electrotransfer to nitrocellulose paper.

The susceptibility of adult schistosomes to immune attrition.

Mouse infection models are described that demonstrate reduction of egg production in Schistosoma haematobium infections and both worm loss and reduced fecundity in S. bovis infections. Neither phenomenon could be shown in S. mansoni infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by serum transfer of the ability to reduce a S. bovis worm burden into immunocompromised hosts. Vaccination with irradiation attenuated parasites was also shown to have consequences for the adults of a challenge infection of S. haematobium and S. bovis specifically. Prior vaccination resulted in an abrogation of the anti-fecundity and adult worm elimination that occurred in non-vaccinated similarly infected mice. These models are being used to define the targets and mechanisms involved in anti-adult attrition. A serological assay, quantitation of a circulating antigen (CAA) has been assessed for its ability to measure worm burdens of different species of schistosome in mice. This assay will be used to question whether anti-adult immunity contributes to the pattern of infection with S. mansoni and S. haematobium in man.

The susceptibility of adult schistosomes to immune attrition

Mouse infection models are described that demonstrate reduction of egg production in Schistosoma haematobium infections and both worm loss and reduced fecundity in S. bovis infections. Neither phenomenum could be shown in S. mansoni infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by the serum transfer of the ability to reduce a S. bovis worm burden into immunocompromised hosts. Vaccination with irradiation attenuated parasites was also shown to have consequences for the adults of a challenge infections of S. haematobium and S. bovis specifically. Prior vaccination resulted in an abrogation of the anti-fecundity and adult worm elimination that occurred in non-vaccinated similary infected mice. hese models are being used to define the targets and mechanisms involved in anti-adult attrition. A serological assay, quantitation of a circulating antigen (CAA) has been assessed for its ability to measure worm burdens of different species of schistosome in mice. This assay will be used to question whether anti-adult immunity contributes to the pattern of infection with S. mansoni and S. haematobium in man