دورية أكاديمية
A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites
| العنوان: | A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites |
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| المؤلفون: | Ben C L van Schaijk, Ivo H J Ploemen, Takeshi Annoura, Martijn W Vos, Lander Foquet, Geert-Jan van Gemert, Severine Chevalley-Maurel, Marga van de Vegte-Bolmer, Mohammed Sajid, Jean-Francois Franetich, Audrey Lorthiois, Geert Leroux-Roels, Philip Meuleman, Cornelius C Hermsen, Dominique Mazier, Stephen L Hoffman, Chris J Janse, Shahid M Khan, Robert W Sauerwein |
| المصدر: | eLife, Vol 3 (2014) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2014. |
| سنة النشر: | 2014 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | Plasmodium, sporozoite, genetically attenuated parasite, malaria, vaccine, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. In this study, we present data on safety and protective efficacy using sporozoites with deletions of two genes, that is the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, PbΔb9ΔslarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high-level protection. The human PfΔb9ΔslarpGAP generated without drug resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a PfΔb9ΔslarpSPZ vaccine. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/03582; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.03582 |
| URL الوصول: | https://doaj.org/article/87e1397d192e42a4b0c5621ba6cad6bd |
| رقم الأكسشن: | edsdoj.87e1397d192e42a4b0c5621ba6cad6bd |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.03582 |