Cross-species Malaria Immunity Induced By Chemically Attenuated Parasites. Good, M. F., Reiman, J. M., Rodriguez, Bibiana, I., Ito, K., Yanow, S. K., El-Deeb, I. M., Batzloff, M. R., Stanisic, D. I., Engwerda, C., Spithill, T., Hoffman, S. L., Lee, M., & McPhun, V. Journal of Clinical Investigation, 123(8):3353--3362, August, 2013.
Paper abstract bibtex Vaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with secocyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite DNA, blocking their ability to replicate. After administration in mice, DNA from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by CD4(+) T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species.
@article{ good_cross-species_2013,
title = {Cross-species Malaria Immunity Induced By Chemically Attenuated Parasites},
volume = {123},
shorttitle = {Cross-species Malaria Immunity Induced By Chemically Attenuated Parasites},
url = {http://digitalcommons.hope.edu/faculty_publications/1019},
abstract = {Vaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with secocyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite {DNA}, blocking their ability to replicate. After administration in mice, {DNA} from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by {CD}4(+) T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species.},
number = {8},
journal = {Journal of Clinical Investigation},
author = {Good, Michael F. and Reiman, Jennifer M. and Rodriguez, I. Bibiana and Ito, Koichi and Yanow, Stephanie K. and El-Deeb, Ibrahim M. and Batzloff, Michael R. and Stanisic, Danielle I. and Engwerda, Christian and Spithill, Terry and Hoffman, Stephen L. and Lee, Moses and McPhun, Virginia},
month = {August},
year = {2013},
pages = {3353--3362}
}
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An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with secocyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite {DNA}, blocking their ability to replicate. After administration in mice, {DNA} from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by {CD}4(+) T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species.},\n number = {8},\n journal = {Journal of Clinical Investigation},\n author = {Good, Michael F. and Reiman, Jennifer M. and Rodriguez, I. 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