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Immunization of rats against Schistosoma mansoni using irradiated cercariae, lung schistosomula and liver-stage worms

Published online by Cambridge University Press:  06 April 2009

M. J. Ford
Affiliation:
Department of Medical Helminthology, Winches Farm Field Station, London School of Hygiene and Tropical Medicine, St Albans, Herts AL4 0XQ
Q. D. Bickle
Affiliation:
Department of Medical Helminthology, Winches Farm Field Station, London School of Hygiene and Tropical Medicine, St Albans, Herts AL4 0XQ
M. G. Taylor
Affiliation:
Department of Medical Helminthology, Winches Farm Field Station, London School of Hygiene and Tropical Medicine, St Albans, Herts AL4 0XQ

Summary

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%).

Type
Research Article
Copyright
Copyright © Cambridge University Press 1984

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References

Attallah, A. M., Smith, A. H., Murrell, K. D., Fleischer, T., Woody, J., Vannier, W. E., Scher, I., Ahmed, A. & Sell, K. W. (1979). Characterization of the immunosuppressive state during Schistosoma mansoni infection. Journal of Immunology 122, 1413–20.CrossRefGoogle ScholarPubMed
Bickle, Q. D. (1982). Studies on the relationship between survival of S. mansoni larvae in mice and the degree of acquired resistance produced. Parasitology 84, 111–22.CrossRefGoogle Scholar
Bickle, Q. D. & Ford, M. J. (1982). Studies on the surface antigenicity and susceptibility to antibody-dependent killing of developing schistosomula using sera from chronically infected mice and mice vaccinated with irradiated cercariae. Journal of Immunology 128, 2101–6.CrossRefGoogle ScholarPubMed
Bickle, Q. D., Bain, J., McGregor, A. & Doenhoff, M. J. (1979 c). Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. (III). The failure of primary infections with cercariae of one sex to induce resistance to reinfection. Transactions of the Royal Society of Tropical Medicine and Hygiene 73, 3741.CrossRefGoogle ScholarPubMed
Bickle, Q. D., Dobinson, T. & James, E. R. (1979 b). The effects of gamma-irradiation on the migration and survival of Schistosoma mansoni in mice. Parasitology 79, 223–30.CrossRefGoogle ScholarPubMed
Bickle, Q. D., Ford, M. J. & Andrews, B. J. (1983). Studies on the development of antischistosomular surface antibodies by mice exposed to irradiated cercariae, adults and/or eggs of S. mansoni. Parasite Immunology 5, 499511.CrossRefGoogle ScholarPubMed
Bickle, Q. D., Taylor, M. G., Doenhoff, M. J. & Nelson, G. S. (1979 a). Immunization of mice with gamma-irradiated intramuscularly injected Schistosoma mansoni. Parasitology 79, 209–22.CrossRefGoogle ScholarPubMed
Boyer, M. H. & Kalfayan, L. I. (1978). Effect of transferred adult S. mansoni on resistance of mice to cercarial challenge. American Journal of Tropical Medicine and Hygiene 27, 542–7.CrossRefGoogle ScholarPubMed
Camus, D., Dessaint, J. P., Fischer, E. & Capron, A. (1979). Non-specific suppressor cell activity and specific cellular unresponsiveness in rat schistosomiasis. European Journal of Immunology 9, 341–4.CrossRefGoogle Scholar
Capron, A., Dessaint, J. P., Capron, M., Joseph, M. & Pestel, J. (1980 a). Role of anaphylactic antibodies in immunity to schistosomes. American Journal of Tropical Medicine and Hygiene 29, 849–57.CrossRefGoogle ScholarPubMed
Capron, M., Carlier, Y., Nzeyimana, H., Minoprio, P., Santoro, F., Sellin, B. & Capron, A. (1980 b). In vitro study of immunological events in human and experimental schistosomiasis: relationships between cytotoxic antibodies and circulating Schistosoma mansoni antigens. Parasite Immunology 2, 223–35.CrossRefGoogle Scholar
Cioli, D., Blum, K. & Ruppel, A. (1978). Schistosoma mansoni: Relationship between parasite age and time of spontaneous elimination from the rat. Experimental Parasitology 45, 7480.CrossRefGoogle ScholarPubMed
Dean, D. A., Cioli, D. & Bukowski, M. A. (1981). Resistance induced by normal and irradiated Schistosoma mansoni. Ability of various worm stages to serve as inducers and targets in mice. American Journal of Tropical Medicine and Hygiene 30, 1026–32.CrossRefGoogle Scholar
Dean, D. A., Minard, P., Stirewalt, M. A., Vannier, W. E. & Murrell, K. D. (1978). Resistance of mice to secondary infection with Schistosoma mansoni. (1). Comparison of bisexual and unisexual initial infections. American Journal of Tropical Medicine and Hygiene 27, 951–6.CrossRefGoogle Scholar
Doenhoff, M., Bickle, Q., Long, E., Bain, J. & McGregor, A. (1978). Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. (1). Demonstration of resistance to reinfection using a model system that involves perfusion of mice within three weeks of challenge. Journal of Helminthology 52, 173–86.CrossRefGoogle Scholar
Erickson, D. G. & Caldwell, W. L. (1965). Acquired resistance in mice and rats after exposure to gamma-irradiated cercariae. American Journal of Tropical Medicine and Hygiene 14, 566–73.CrossRefGoogle Scholar
Hsu, S. Y. L., Hsu, H. F. & Burmeister, L. F. (1981). Schistosoma mansoni: Vaccination of mice with highly X-irradiated cercariae. Experimental Parasitology 52, 91104.CrossRefGoogle ScholarPubMed
Knopf, P. M. & Cioli, D. (1980). Schistosoma mansoni: resistance to an infection with cercariae induced by the transfer of live adult worms to the rat. International Journal for Parasitology 10, 1319.CrossRefGoogle Scholar
Knopf, P. M., Mangold, B. L. & Makari, G. J. (1983). Recovery of parasites at different stages of migration following infection of rats with S. mansoni. Parasitology 86, 3749.CrossRefGoogle Scholar
Knopf, P. M., Nutman, T. B. & Reasoner, J. P. (1977). Schistosoma mansoni: Resistance to reinfection in the rat. Experimental Parasitology 41, 7482.CrossRefGoogle ScholarPubMed
Long, E., Doenhoff, M. & Bain, J. (1978). Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. 2. The time at which resistance to reinfection develops. Journal of Helminthology 52, 187–91.CrossRefGoogle ScholarPubMed
Mangold, B. L. & Dean, D. A. (1983). Autoradiographic analysis of Schistosoma mansoni migration from the skin to lungs in naive mice. Evidence that most attrition occurs after the skin phase. American Journal of Tropical Medicine and Hygiene 32, 785–9.CrossRefGoogle ScholarPubMed
Mangold, B. L. & Knopf, P. M. (1978). The effect of assay conditions on the recovery of schistosomula from the lungs of normal and resistant rats infected with Schistosoma mansoni. Journal of Parasitology 64, 813–21.CrossRefGoogle ScholarPubMed
Mastin, A. J., Bickle, Q. D. & Wilson, R. A. (1983). Schistosoma mansoni: migration and attrition of irradiated and challenge schistosomula in the mouse. Parasitology 87, 87102.CrossRefGoogle ScholarPubMed
Mazingue, C., Camus, D., Dessaint, J. P., Capron, M. & Capron, A. (1980). In vitro and in vivo inhibition of mass cell degranulation by a factor from Schistosoma mansoni. International Archives of Allergy and Applied Immunology 63, 178–89.CrossRefGoogle Scholar
Minard, P., Dean, D. A., Jacobson, R. H., Vannier, W. E. & Murrell, K. D. (1978). Immunization of mice with Cobalt-60 irradiated Schistosoma mansoni cercariae. American Journal of Tropical Medicine and Hygiene 27, 7686.CrossRefGoogle ScholarPubMed
Mota-Santos, T. A., Tavares, C. A. P., Gazzinelli, G. & Pellegrino, J. (1977). Immuno-suppression mediated by adult worms in chronic schistosomiasis mansoni. American Journal of Tropical Medicine and Hygiene 26, 727–31.CrossRefGoogle Scholar
Murrell, K. D., Clark, S., Dean, D. A. & Vannier, W. E. (1979). Influence of mouse strain on induction of resistance with irradiated Schistosoma mansoni cercariae. Journal of Parasitology 65, 829–31.CrossRefGoogle ScholarPubMed
Perez, H., Clegg, J. A. & Smithers, S. R. (1974). Acquired immunity to S. mansoni in the rat: measurement of immunity by lung recovery technique. Parasitology 69, 349–59.CrossRefGoogle Scholar
Phillips, S. M., Reid, W. A., Bruce, J. I., Hedlund, K., Colvin, R. C., Campbell, R., Diggs, C. L. & Sadun, E. H. (1975). The cellular and humoral immune response to Schistosoma mansoni infection in inbred rats. (I). Mechanisms during initial exposure. Cellular Immunology 19, 99116.CrossRefGoogle Scholar
Phillips, S. M., Reid, W. A., Doughty, B. L. & Khoury, P. B. (1978). The cellular and humoral immune response to Schistosoma mansoni infection in inbred rats. (III). Development of optimal protective immunity following natural infection and artificial immunisation. Cellular Immunology 38, 225–38.CrossRefGoogle Scholar
Phillips, S. M., Reid, W. A. & Sadun, E. H. (1977). The cellular and humoral immune response to Schistosoma mansoni infection in inbred rats. (II). Mechanisms during re-exposure. Cellular Immunology 28, 7589.CrossRefGoogle Scholar
Ramalho-Pinto, F. J., Smithers, S. R. & Playfair, J. H. L. (1979). Carrier effect during the course of experimental schistosomiasis: suppression of the response to TNP-schistosomula in rats and inbred mice. Journal of Immunology 123, 507–14.CrossRefGoogle ScholarPubMed
Sher, A. & Benno, D. (1982). Decreasing immunogenicity of developing schistosome larvae. Parasite Immunology 4, 101–7.CrossRefGoogle ScholarPubMed
Smithers, S. R. (1968). Immunity to blood helminths. In Immunity to Parasites, Sixth Symposium of the British Society for Parasitology (ed. Taylor, A. E. R.), pp. 5566. Oxford: Blackwell Scientific Publications.Google Scholar
Smithers, S. R. (1972). Recent advances in the immunology of schistosomiasis. British Medical Bulletin 28, 4954.CrossRefGoogle ScholarPubMed
Smithers, S. R. (1976). Immunity to trematode infections. In Immunology of Parasitic Infections (ed. Cohen, S. and Sadun, E. H), pp. 296332. Oxford: Blackwell Scientific Publications.Google Scholar
Smithers, S. R. & Terry, R. J. (1965 a). Naturally acquired resistance to experimental infection of S. mansoni in the albino rat. Parasitology 55, 711–17.CrossRefGoogle Scholar
Smithers, S. R. & Terry, R. J. (1965 b). The infection of laboratory hosts with cercariae of S. mansoni and the recovery of the adult worms. Parasitology 55, 695700.CrossRefGoogle Scholar
Smithers, S. R. & Terry, R. J. (1967). Resistance to experimental infection in rhesus monkeys induced by the transfer of adult worms. Transactions of the Royal Society of Tropical Medicine and Hygiene 61, 517–23.CrossRefGoogle ScholarPubMed
Smithers, S. R. & Terry, R. J. (1969). The immunology of schistosomiasis. Advances in Parasitology 7, 4193.CrossRefGoogle ScholarPubMed
Taylor, M. G. & Bickle, Q. D. (1980). Progress in the development of radiation-attenuated vaccines for schistosomiasis. International Journal of Nuclear Medicine and Biology 7, 97103.CrossRefGoogle ScholarPubMed