These studies address current controversies over the site(s) of challenge attrition in the murine irradiated vaccine model of immunity to Schistosoma mansoni. Two possibilities have been investigated. Firstly, that the site of death of the radiation-attenuated schistosomes used to vaccinate the mice may vary in different laboratories and secondly, that the skin sites selected for presentation of the immunizing and challenge parasites may influence the final site at which immunity is effected (i.e. ear/abdomen vs tail/tail). The migration of radiolabelled cercariae exposed to 0, 20 or 50 krad of gamma irradiation from the NIMR 60Cobalt source was examined in CBA/Ca mice by squashed organ autoradiography. Unirradiated parasites all migrated from the skin to the lungs, and 65% moved on to the liver. Migration of parasites attenuated by exposure to 20 krad of gamma irradiation was delayed, but 76% finally reached the lungs; only 1% was recruited to the liver. The majority of 50 krad attenuated parasites died in the skin, with only 4% accomplishing migration to the pulmonary vasculature. The major site of death (and by implication of antigenic stimulation) of the 20 krad attenuated NIMR strain S. mansoni used routinely for vaccination purposes in our laboratory, is thus the lungs, a finding that does not explain the fact that immunity is mediated primarily in the skin in our model system. Site elimination experiments and squashed organ autoradiography showed conclusively that, irrespective of the skin sites chosen for presentation of the immunizing and challenge population of worms, NIMR challenge parasites are killed predominantly in the skin of vaccinated CBA/Ca mice. Moreover, qualitative and quantitative histological examination of the challenged tail skin of vaccinated mice revealed that inflammatory reactions comprising mononuclear cells and eosinophils develop in this site and function to trap and eliminate challenge larvae, despite a reported reduction in antigen presenting cells in this region.

Laboratory rodents vaccinated with highly irradiated cercariae of Schistosoma mansoni develop significant levels of specific acquired resistance yet effect challenge elimination in different organs. Mice and guinea-pigs are at opposite ends of the spectrum in this respect since, in our hands, vaccinated mice kill challenge parasites in the skin whereas vaccinated guinea-pigs kill challenge parasites predominantly in the liver. To determine whether this phenomenon is host-dependent (site) or parasite-dependent (stage), we have transferred worms harvested from mice or guinea-pigs into vaccinated recipient guinea-pigs. The results show that mouse-derived 5-day lung worms and 9-day liver worms that are essentially refractory to vaccine resistance in mice are indeed susceptible to vaccine resistance in guinea-pigs. Identical levels of susceptibility were recorded for lung-stage larvae introduced via the foot vein so as to experience lung and liver mechanisms, or via the mesenteric vein to bypass the lung, thereby confirming that vaccine resistance in guinea-pigs operates in the liver. Mouse worms and guinea-pig worms exhibited equivalent levels of susceptibility at all stages of development. Thirteen-day-old larvae from either donor species were on the border-line of vulnerability, while 20-day-old worms were totally refractory to vaccine immunity in guinea-pigs. These data show that vaccine immunity in different rodent species is a site-dependent, rather than a stage-dependent phenomenon. There is, however, an upper age limit of schistosome vulnerability which is common to worms harvested from different donor species.