期刊
CELL REPORTS
卷 21, 期 10, 页码 2868-2878出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.11.024
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资金
- MRC [MR/N00227X/1]
- PATH-MVI
- NIH [GM122565, GM56778]
- Medical Research Council [MR/N00227X/1] Funding Source: researchfish
- MRC [MR/N00227X/1] Funding Source: UKRI
Inhibiting transmission of Plasmodium is a central strategy in malarial eradication, and the biological process of gamete fusion during fertilization is a proven target for this approach. The lack of a structure or known molecular function of current anti-malarial vaccine targets has previously been a hindrance in the development of transmission-blocking vaccines. Structure/function studies have indicated that the conserved gamete membrane fusion protein HAP2 is a class II viral fusion protein. Here, we demonstrate that targeting a function-critical site of the fusion/cd loop with species-specific antibodies reduces Plasmodium berghei transmission in vivo by 58.9% and in vitro fertilization by up to 89.9%. A corresponding reduction in P. falciparum transmission (75.5%/36.4% reductions in intensity/prevalence) is observed in complimentary field studies. These results emphasize conserved mechanisms of fusion in Apicomplexa, while highlighting an approach to design future anti-malarial transmission-blocking vaccines.
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