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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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. Angrisano et al. find that the HAP2 cd-loop can be targeted as an anti-malarial intervention, is immunogenic across multiple plasmodial species, can induce antibodies that specifically recognize the sexual stages of the parasitic life cycle, and can mediate transmission-blocking immunity in the lab and the field.

Original languageEnglish (US)
Pages (from-to)2868-2878
Number of pages11
JournalCell Reports
Volume21
Issue number10
DOIs
StatePublished - Dec 5 2017

Fingerprint

Plasmodium berghei
Antimalarials
Plasmodium falciparum
Fusion reactions
Germ Cells
Vaccines
Membrane Fusion Proteins
Viral Fusion Proteins
Apicomplexa
Malaria Vaccines
Biological Phenomena
Plasmodium
Antibodies
Fertilization in Vitro
Life Cycle Stages
Fertilization
Immunity
Life cycle

Keywords

  • fusion
  • HAP2
  • malaria
  • transmission
  • vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Targeting the Conserved Fusion Loop of HAP2 Inhibits the Transmission of Plasmodium berghei and falciparum. / Angrisano, Fiona; Sala, Katarzyna A.; Da, Dari F.; Liu, Yanjie; Pei, Jimin; Grishin, Nick V.; Snell, William J.; Blagborough, Andrew M.

In: Cell Reports, Vol. 21, No. 10, 05.12.2017, p. 2868-2878.

Research output: Contribution to journalArticle

Angrisano, Fiona ; Sala, Katarzyna A. ; Da, Dari F. ; Liu, Yanjie ; Pei, Jimin ; Grishin, Nick V. ; Snell, William J. ; Blagborough, Andrew M. / Targeting the Conserved Fusion Loop of HAP2 Inhibits the Transmission of Plasmodium berghei and falciparum. In: Cell Reports. 2017 ; Vol. 21, No. 10. pp. 2868-2878.
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