| Literature DB >> 28053159 |
James G Kublin1,2,3, Sebastian A Mikolajczak4, Brandon K Sack4, Matt E Fishbaugher4, Annette Seilie5, Lisa Shelton4, Tracie VonGoedert4, Melike Firat4, Sara Magee4, Emma Fritzen4, Will Betz4, Heather S Kain4, Dorender A Dankwa4, Ryan W J Steel4, Ashley M Vaughan4, D Noah Sather4, Sean C Murphy4,5,6, Stefan H I Kappe1,2.
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.Entities:
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Year: 2017 PMID： 28053159 DOI： 10.1126/scitranslmed.aad9099
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956