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Cell Rep. 2017 Dec 5;21(10):2868-2878. doi: 10.1016/j.celrep.2017.11.024.

Targeting the Conserved Fusion Loop of HAP2 Inhibits the Transmission of Plasmodium berghei and falciparum.

Author information

1
Department of Life Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK. Electronic address: f.angrisano14@imperial.ac.uk.
2
Department of Life Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK.
3
Institut de Recherche en Sciences de la Santé (IRSS), Bobo Dioulasso, Burkina Faso.
4
Department of Cell Biology and Molecular Genetics, University of Maryland, 4066 Campus Dr., College Park, Maryland 20742, USA.
5
Department of Biophysics and Biochemistry, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard Dallas, TX 75390-9039, USA.
6
Department of Cell Biology and Molecular Genetics, University of Maryland, 4066 Campus Dr., College Park, Maryland 20742, USA. Electronic address: wsnell1@umd.edu.
7
Department of Life Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK. Electronic address: a.blagborough@imperial.ac.uk.

Abstract

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.

KEYWORDS:

HAP2; fusion; malaria; transmission; vaccine

PMID:
29212032
PMCID:
PMC5732318
DOI:
10.1016/j.celrep.2017.11.024
[Indexed for MEDLINE]
Free PMC Article

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