Disruption of Plasmodium falciparum development by antibodies against a conserved mosquito midgut antigen

Rhoel R. Dinglasan, Dario E. Kalume, Stefan M. Kanzok, Anil K. Ghosh, Olga Muratova, Akhilesh Pandey, Marcelo Jacobs-Lorena

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Malaria parasites must undergo development within mosquitoes to be transmitted to a new host. Antivector transmission-blocking vaccines inhibit parasite development by preventing ookinete interaction with mosquito midgut ligands. Therefore, the discovery of novel midgut antigen targets is paramount. Jacalin (a lectin) inhibits ookinete attachment by masking glycan ligands on midgut epithelial surface glycoproteins. However, the identities of these midgut glycoproteins have remained unknown. Here we report on the molecular characterization of an Anopheles gambiae aminopeptidase N (AgAPN1) as the predominant jacalin target on the mosquito midgut luminal surface and provide evidence for its role in ookinete invasion. α-AgAPN1 IgG strongly inhibited both Plasmodium berghei and Plasmodium falciparum development in different mosquito species, implying that AgAPN1 has a conserved role in ookinete invasion of the midgut. Molecules targeting single midgut antigens seldom achieve complete abrogation of parasite development. However, the combined blocking activity of α-AgAPN1 IgG and an unrelated inhibitory peptide, SM1, against P. berghei was incomplete. We also found that SM1 can block only P. berghei, whereas α-AgAPN1 IgG can block both parasite species significantly. Therefore, we hypothesize that ookinetes can evade inhibition by two potent transmission-blocking molecules, presumably through the use of other ligands, and that this process further partitions murine from human parasite midgut invasion models. These results advance our understanding of malaria parasite-mosquito host interactions and guide in the design of transmission-blocking vaccines.

Original languageEnglish (US)
Pages (from-to)13461-13466
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number33
DOIs
StatePublished - Aug 14 2007
Externally publishedYes

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Keywords

  • Glycan
  • Malaria
  • Mass spectrometry
  • Transmission-blocking vaccine

ASJC Scopus subject areas

  • Genetics
  • General

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