Publications & Reports

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

Fiona Angrisano, Katarzyna A Sala, Dari F Da, Yanjie Liu, Jimin Pei, Nick V Grishin, William J Snell, Andrew M Blagborough
Department of Life Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK. Electronic address: [email protected]

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.

Link to publisher’s web site

Publication

  • Journal: Cell Reports
  • Published: 05/12/2017
  • Volume: 21
  • Issue: 10
  • Pagination: 2868-2878

Author