Immunization of rats againstSchistosoma mansoniusing irradiated cercariae, lung schistosomula and liver-stage worms

Abstract

In PVG rats a single immunizing infection with Schistosoma mansoni cercariae exposed to 0, 5, 10 or 20 krad. gamma radiation failed to induce more than minimal resistance (17-29%) to challenge 4 weeks later, whereas 4 immunizations with 20 krad.-irradiated cercariae, over several months, induced substantial resistance (75%). In contrast, significant protection was induced in Fischer rats by a single immunization with unirradiated cercariae or cercariae irradiated with up to 80 krad. Comparable resistance was induced by unirradiated and by 2, 5 and 20 krad.-irradiated cercariae (67-74%) and lower levels by 10, 40 and 80 krad.-irradiated infections (57, 48 and 33%, respectively). Although the resistance induced by a single dose of 1000 20 krad.-irradiated cercariae could be boosted by a second (88%), further immunizations failed to enhance this resistance. Also, increasing the number of immunizing cercariae in single or multiple vaccinations from 1000 to 3000 failed to increase the resistance. While the resistance induced by 20 krad.-irradiated cercariae persisted undiminished for at least 25 weeks (67%), the resistance induced by normal cercariae declined to insignificant levels by 25 weeks (21%). Comparison of the migration and survival of unirradiated and of 20 and 40 krad.-irradiated cercariae revealed dramatic differences in their fate: parasites exposed to 40 krad. remained in the skin, while the majority of 20 krad.-irradiated parasites died in the lungs after a sojourn of at least 14 days. Thus, although skin schistosomula alone could induce significant protection, optimal resistance was induced only by parasites which migrated to the lungs or beyond. The immunizing potential of these older parasites was investigated by exposing rats to lung- and liver-stage larvae injected into the tail and mesenteric veins, respectively. Irradiated 4-day lung schistosomula induced comparable resistance (79%) to that induced by a complete unattenuated cercarial infection (78%), whereas less resistance was induced by irradiated and unirradiated 11-day-old liver worms (30 and 27%) and by 25-day-old pre-adult worms (48%).

Vaccines to combat the neglected tropical diseases

“…The radiation‐attenuated vaccine has also been used in many different host species and against S. mansoni , S. haematobium , Schistosoma bovis, and S. japonicum (134–137). The radiation‐attenuated vaccine for S. mansoni has been shown to protect in a variety of host species such as rats (138) and non‐human primates, including baboons and chimpanzees (139, 140). Radiation‐attenuated larvae of S. haematobium induce protection in baboons (141).…”

Immunity induced by the radiation‐attenuated schistosome vaccine

“…14–17). The RA vaccine for S. mansoni also protects other host species such as rats (18) and non‐human primates including baboons and chimpanzees (e.g. 19–21), while RA larvae of S. haematobium induce protection in baboons (22).…”

SjHSP70, a recombinant Schistosoma japonicum heat shock protein 70, is immunostimulatory and induces protective immunity against cercarial challenge in mice

“…Highly effective and safe prophylactic vaccines are urgently required for the sustainable control of schistosomiasis. Previous studies have shown that high levels of protective immunity can be induced in animals such as mice, rats, cattle, pigs, and rhesus monkeys, immunized with radiation-attenuated (RA) Schistosoma cercariae or schistosomula (Majid et al 1980;Jwo and LoVerde 1989;Ford et al 1984;Harrison et al 1990;Lin et al 2011). However, the application of RA vaccines is unfeasible because they are unsafe and resources of schistosome larvae are unavailable.…”