The migration and survival of gamma-irradiatedSchistosoma mansonilarvae and the duration of host—parasite contact in relation to the induction of resistance in mice

Abstract

SUMMARYThe migration in mice of 20, 50 and 90 krad. 60Co-irradiated Schistosoma mansoni larvae, biosynthetically radio-isotope labelled with [75Se]-selenomethionine, was evaluated by autoradiography of compressed tissues and compared to the migration of non-irradiated 75Se-labelled larvae. The migration of 20 krad. -irradiated schistosomula between skin and lungs was slightly delayed but otherwise paralleled the migration of normal, non-irradiated schistosomula during the first 8 days following exposure. By day 8 over 90% of both non-irradiated and 20 krad. -irradiated organises were located in the lungs. In contrast to non-irradiated organisms, however, only a small proportion of 20 krad. organisms migrated to the liver. The delay in migration between skin and lungs was more pronounced with 50 krad. -irradiated schistosomula. Nevertheless, 45–93% of 50 krad. -irradiated organisms migrated to the lungs by 8 days post-exposure. Over 90% of the 50 krad. larvae detected in the mouse on day 21 were in the lungs; no more than an occasional 50 krad.-irradiated organism was ever detected in the liver. In three experiments, over 85% of the 90 krad. -irradiated organisms were retained in the skin; in a fourth experiment about half of the 90 krad. -irradiated organisms migrated as far as the lungs. As with 50 krad. organisms, only an occasional 90 krad. organism was ever detected in the liver. Removal of the skin exposure site within the first 4 days of immunization with either 50 or 90 krad. -irradiated cercariae completely blocked the induction of resistance. Removal between the 4th and 6th days gave variable results. Mice had to be in contact with the irradiated larvae for a minimum of 8–11 days to stimulate a level of resistance comparable to that of mice whose immunization site was not removed.

Immunity induced by the radiation‐attenuated schistosome vaccine

“…The dose of gamma radiation required to induce maximal levels of protection differs between laboratories but is usually between ∼20 krad (e.g. 12,14,29), and 50 krad (10,30). A single exposure to 500 optimally RA cercariae is sufficient to achieve protection of up to 60–70%, and exposure to multiple doses can result in slightly higher levels of protection (e.g.…”

“…It appears that immune priming in all three of these locations is crucial for protection. Excision of either the skin site of exposure (30), or the sdLN (41), within days after vaccination, reduces the level of protection that can be generated. However, immune priming in the skin alone is insufficient, since parasites hyper‐irradiated with 80 krad do not migrate to the lungs, nor induce protection (42,43).…”

A Meta-Analysis of Experimental Studies of Attenuated Schistosoma mansoni Vaccines in the Mouse Model

“…The lower irradiation doses enable attenuated parasites to live longer in the vaccinated host. After vaccination, irradiated cercariae have been reported to be present around the skin exposure site for approximately 4 days and then gradually moved to the lungs where they transformed from cercariae into lung-stage schistosomula ( 60 ). It has been reported that the immunizing parasite has to reach the lungs and transform to lung-stage schistosomula to elicit protective immunity against challenge infection ( 60 , 61 ), which may not be the case for cercariae attenuated with high doses of ionizing radiation.…”

“…After vaccination, irradiated cercariae have been reported to be present around the skin exposure site for approximately 4 days and then gradually moved to the lungs where they transformed from cercariae into lung-stage schistosomula ( 60 ). It has been reported that the immunizing parasite has to reach the lungs and transform to lung-stage schistosomula to elicit protective immunity against challenge infection ( 60 , 61 ), which may not be the case for cercariae attenuated with high doses of ionizing radiation. Several studies have reported that non-attenuated challenge cercariae in vaccinated mice slowly move to the lungs and then gradually disappear ( 61 , 62 ).…”

“…Several studies have reported that non-attenuated challenge cercariae in vaccinated mice slowly move to the lungs and then gradually disappear ( 61 , 62 ). Several studies report that cercariae exposed to extremely high irradiation doses will die in the host skin before they start to migrate inside the host body ( 60 , 63 ). Mountford et al reported that hosts needed to be exposed to both highly irradiated cercariae, which die in the host skin, and lung-stage schistosome parasites to elicit protective immunity ( 64 ).…”