1. Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects.
- Author
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Kublin JG, Mikolajczak SA, Sack BK, Fishbaugher ME, Seilie A, Shelton L, VonGoedert T, Firat M, Magee S, Fritzen E, Betz W, Kain HS, Dankwa DA, Steel RW, Vaughan AM, Noah Sather D, Murphy SC, and Kappe SH
- Subjects
- Adult, Animals, Antibodies, Protozoan blood, Female, Gene Deletion, Genetic Engineering, Humans, Immunoglobulin G blood, Malaria Vaccines genetics, Male, Mice, Mice, Inbred BALB C, Middle Aged, Plasmodium falciparum immunology, Protozoan Proteins genetics, Sporozoites immunology, Vaccines, Attenuated genetics, Vaccines, Attenuated immunology, Young Adult, Malaria Vaccines immunology, Malaria, Falciparum prevention & control, Plasmodium falciparum genetics, Sporozoites genetics
- Abstract
Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52
- /p36- /sap1- ). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers. Pf GAP3KO sporozoites were delivered to 10 volunteers using infected mosquito bites with a single exposure consisting of 150 to 200 bites per subject. All subjects remained blood stage-negative and developed inhibitory antibodies to sporozoites. GAP3KO rodent malaria parasites engendered complete, protracted immunity against infectious sporozoite challenge in mice. The results warrant further clinical testing of Pf GAP3KO and its potential development into a vaccine strain., (Copyright © 2017, American Association for the Advancement of Science.)- Published
- 2017
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