Genetically modified Plasmodium parasites as a protective experimental malaria vaccine

被引:400
作者
Mueller, AK
Labaied, M
Kappe, SHI
Matuschewski, K
机构
[1] Seattle Biomed Res Inst, Seattle, WA 98109 USA
[2] Univ Heidelberg, Sch Med, Dept Parasitol, D-69120 Heidelberg, Germany
[3] Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature03188
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes(1), transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites(2). Liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection(3). Using expression profiling, we previously identified genes that are only expressed in the pre-erythrocytic stages of the parasite(4,5). Here, we show by reverse genetics that one identified gene, UIS3 (upregulated in infective sporozoites gene 3), is essential for early liver-stage development. uis3-deficient sporozoites infect hepatocytes but are unable to establish blood-stage infections in vivo, and thus do not lead to disease. Immunization with uis3-deficient sporozoites confers complete protection against infectious sporozoite challenge in a rodent malaria model. This protection is sustained and stage specific. Our findings demonstrate that a safe and effective, genetically attenuated whole-organism malaria vaccine is possible.
引用
收藏
页码:164 / 167
页数:4
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