- Email: [email protected]
Application of nuclear technology to the development of a vaccine against sporozoite-induced malaria
166
Around
the Nuclear
World
References 1. Radiosterilization of Medical Products and Recommended Code of Practice. Pub. No. ST],; PUB/157. IAEA, Vienna (1967). 2. Manual on Radiation Sterilization of Medical and Biological Materials IAEA Pub. No. ST11 DOG/149. IAEA, Vienna (1973). 3. Radiation Sterilization-Irradiated Tissues and their Potential Clinical Use. Proceedings of an IAEA Advisory Group, Athens, 1976 (Edited by PHILLIPSCi. O., TALLENTIREA. and TRIANTAFYLLOU N.). North E Wales Institute, Clwyd, U.K. (1978).
Application of Nuclear Technology to the Development of a Vaccine Against Sporozoite-induced Malaria ALAN H. COCHRANJZ Assistant Professor, New York University Medical Center, Division of Parasitology, Department Microbiology
of
The sporozoite stage of malaria parasites has been used in vaccination attempts involving a variety of mammalian hosts. Mice have been immunized and protected with radiation-attenuated sporozoites of Plasmodium berghei and P. chabaudi; a relatively small number of rhesus monkeys have been immunized with irradiated sporozoites of either P. cynomolgi or P. knowlesi; and finally, a small number of humans have been successfully immunized by the bites of irradiated P. vivax or P. falciparum-infected mosquitoes. Intact irradiated or viable sporozoites are, at present, the most effective sporozoite antigen preparation for vaccination purposes. They are highly immunogenic and when administered either intravenously or by the bites of infected mosquitoes, confer complete protection against sporozoiteinduced malaria infections without the need for immunopotentiation. In rodents complete protection can be obtained following immunization with a single dose of irradiated sporozoites. Induction of protective immunity in rhesus monkeys and humans, however, requires the administration of larger numbers of sporozoites in multiple immunizing doses. Successful vaccination against sporozoites is characterized by development of a sterile immunity which is strictly stage specific. Immunized hosts, while totally resistant to sporozoite challenge, are fully susceptible to challenge with blood stages of the malaria parasite. In sporozoite-vaccinated rhesus monkeys and humans, protection, as well as antisporozoite antibodies, is strictly species specific. Immunized primates are protected only against challenge with sporozoites of the plasmodial species used for immunization. These immunized hosts are however fully resistant to challenge with sporozoites of various strains of the homologous species. This protection is accompanied by the development of species-specific antibodies which show cross-strain reactivity for a given plasmodial species. In contrast, in sporozoite-immunized rodents, protection and antisporozoite antibodies appear to be less species specific. Both cell-mediated and humoral immune responses play a role in sporozoite-induced immunity. In rodents, the transfer of immune spleen cells confers protection to naive recipient mice, and, in addition, ~-suppressed mice have been successfully immunized. Following incubation with immune serum from sporozoite-immunized and protected simian or rodent hosts sporozoites lose their infectivity. The passive transfer of rodent immune serum decreases both the circulation time and the number of sporozoites which develop into exo-erythrocytic stages. A hybrid cell line, formed by the fusion of spleen cells of P. berghei sporozoite-immunized mice with a mouse plasmacytoma, secretes antisporozoite antibodies in vitro. These monospecific antibodies are directed against a functional, species-specific protective surface antigen. This antigen has been characterized by radiolabeling of the sporozoite surface membrane, or by metabolic labeling of the parasites, followed by immunoprecipitation of the parasite extract and acrylamide gel electrophoresis. Metabolically-labeled sporozoites in addition remain fully infective and are being used to follow early sporozoite-host cell interaction. The hybridoma tech&logy and labeling techniques, once fully developed in the rodent and simian malaria sysmms, should be applicable to human malaria sporozoites, and will hopefully solve the problems of antigen source for vaccination purposes.
Around
the Nuclear
World
References 1. Radiosterilization of Medical Products and Recommended Code of Practice. Pub. No. ST],; PUB/157. IAEA, Vienna (1967). 2. Manual on Radiation Sterilization of Medical and Biological Materials IAEA Pub. No. ST11 DOG/149. IAEA, Vienna (1973). 3. Radiation Sterilization-Irradiated Tissues and their Potential Clinical Use. Proceedings of an IAEA Advisory Group, Athens, 1976 (Edited by PHILLIPSCi. O., TALLENTIREA. and TRIANTAFYLLOU N.). North E Wales Institute, Clwyd, U.K. (1978).
Application of Nuclear Technology to the Development of a Vaccine Against Sporozoite-induced Malaria ALAN H. COCHRANJZ Assistant Professor, New York University Medical Center, Division of Parasitology, Department Microbiology
of
The sporozoite stage of malaria parasites has been used in vaccination attempts involving a variety of mammalian hosts. Mice have been immunized and protected with radiation-attenuated sporozoites of Plasmodium berghei and P. chabaudi; a relatively small number of rhesus monkeys have been immunized with irradiated sporozoites of either P. cynomolgi or P. knowlesi; and finally, a small number of humans have been successfully immunized by the bites of irradiated P. vivax or P. falciparum-infected mosquitoes. Intact irradiated or viable sporozoites are, at present, the most effective sporozoite antigen preparation for vaccination purposes. They are highly immunogenic and when administered either intravenously or by the bites of infected mosquitoes, confer complete protection against sporozoiteinduced malaria infections without the need for immunopotentiation. In rodents complete protection can be obtained following immunization with a single dose of irradiated sporozoites. Induction of protective immunity in rhesus monkeys and humans, however, requires the administration of larger numbers of sporozoites in multiple immunizing doses. Successful vaccination against sporozoites is characterized by development of a sterile immunity which is strictly stage specific. Immunized hosts, while totally resistant to sporozoite challenge, are fully susceptible to challenge with blood stages of the malaria parasite. In sporozoite-vaccinated rhesus monkeys and humans, protection, as well as antisporozoite antibodies, is strictly species specific. Immunized primates are protected only against challenge with sporozoites of the plasmodial species used for immunization. These immunized hosts are however fully resistant to challenge with sporozoites of various strains of the homologous species. This protection is accompanied by the development of species-specific antibodies which show cross-strain reactivity for a given plasmodial species. In contrast, in sporozoite-immunized rodents, protection and antisporozoite antibodies appear to be less species specific. Both cell-mediated and humoral immune responses play a role in sporozoite-induced immunity. In rodents, the transfer of immune spleen cells confers protection to naive recipient mice, and, in addition, ~-suppressed mice have been successfully immunized. Following incubation with immune serum from sporozoite-immunized and protected simian or rodent hosts sporozoites lose their infectivity. The passive transfer of rodent immune serum decreases both the circulation time and the number of sporozoites which develop into exo-erythrocytic stages. A hybrid cell line, formed by the fusion of spleen cells of P. berghei sporozoite-immunized mice with a mouse plasmacytoma, secretes antisporozoite antibodies in vitro. These monospecific antibodies are directed against a functional, species-specific protective surface antigen. This antigen has been characterized by radiolabeling of the sporozoite surface membrane, or by metabolic labeling of the parasites, followed by immunoprecipitation of the parasite extract and acrylamide gel electrophoresis. Metabolically-labeled sporozoites in addition remain fully infective and are being used to follow early sporozoite-host cell interaction. The hybridoma tech&logy and labeling techniques, once fully developed in the rodent and simian malaria sysmms, should be applicable to human malaria sporozoites, and will hopefully solve the problems of antigen source for vaccination purposes.