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Maintenance of protective immunity against malaria by persistent hepatic parasites derived from irradiated sporozoites


, : Maintenance of protective immunity against malaria by persistent hepatic parasites derived from irradiated sporozoites. Proceedings of the National Academy of Sciences of the United States of America 92(9): 4066-4068

Immunization of rodents and humans with irradiation-attenuated malaria sporozoites confers preerythrocytic stage-specific protective immunity to challenge infection. This immunity is directed against intrahepatic parasites and involves T cells and interferon gamma, which prevent development of exoerythrocytic stages and subsequent blood infection. The present study was undertaken to determine how protective immunity is achieved after immunization of rodent hosts with irradiated Plasmodium berghei sporozoites. We present evidence that irradiated parasites persist in hepatocytes of rats and mice for up to 6 months after immunization. A relationship between the persistence of parasites and the maintenance of protective immunity was observed. Protective immunity was abrogated in irradiated-sporozoite-immunized rats following the application of chemotherapy to remove preexisting liver parasites. Additionally, protective immunity against sporozoite challenge was established in rats vaccinated with early and late hepatic stages of irradiated parasites. These results show that irradiation-attenuated sporozoites produce persistent intrahepatic stages in vivo necessary for the induction and maintenance of protective immunity.

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Accession: 002889032

PMID: 7732032

DOI: 10.1073/pnas.92.9.4066

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Related references

Vanderberg, J.P.; Nussenzweig, R.S.; Most, H.; Orton, C.G., 1968: Protective immunity produced by the injection of X-irradiated sporozoites of Plasmodium berghei. 2. Effects of radiation on sporozoites. Journal of Parasitology, 54: 1175-1180

Vanderberg, J.P.; Nussenzweig, R.S.; Most, H.; Orton, C.G., 1968: Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. II. Effects of radiation on sporozoites. Journal of Parasitology 54(6): 1175-1180

Vanderberg J.P.; Nussenzweig R.S.; Most H.; Orton C.G., 1968: Protective immunity produced by the injection of x irradiated sporozoites of plasmodium berghei ii effects of radiation on sporozoites mouse. Journal of Parasitology 54(6): 1175-1180

Vanderberg, J.; Nussenzweig, R.; Most, H., 1969: Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. V. In vitro effects of immune serum on sporozoites. Military Medicine 134(10): 1183-1190

Nussler, A.K.; Rénia, L.; Pasquetto, V.; Miltgen, F.; Matile, H.; Mazier, D., 1993: In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants. It has been known for many years that the injection of irradiated sporozoites renders mice immune to a subsequent challenge with viable sporozoites. The precise mechanisms whereby invading live sporozoites are killed have remained obscure, althoug...

Nussler, A.K.; Renia, L.; Pasquetto, V.; Miltgen, F.; Matile, H.; Mazier, D., 1993: In vivo induction of the nitric oxide pathway in hepatocytes after infection with irradiated malaria sporozoites, malaria blood parasites of adjuvants. The mechanisms responsible for malarial immunity induced by repetitive injections of X-irradiated sporozoites have not been fully established. We demonstrate here that a single injection of irradiated sporozoites induced, as soon as 24 h after, a...

Nussenzweig, R.; Vanderberg, J.; Most, H., 1969: Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. IV. Dose response, specificity and humoral immunity. Military Medicine 134(10): 1176-1182

Nussenzweig R.S.; Vanderberg J.; Most H.; Orton C., 1970: Immunity in simian malaria induced by irradiated sporozoites. Journal of Parasitology 56(4 SEC II PT 1): 252

Nussenzweig, V.; Nussenzweig, R.S., 1984: Protective immunity to malaria sporozoites. The rationale for the development of a malaria vaccine based on the use of sporozoites is discussed with reference to studies on circumsporozoite proteins, the most immunogenic constituent of sporozoites.

Nussenzweig, R.S.; Vanderberg, J.; Most, H.; Orton, C., 1967: Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature 216(5111): 160-162