Identification of GAP DH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion

Sung Jae Cha, Min Sik Kim, Akhilesh Pandey, Marcelo Jacobs-Lorena

Research output: Contribution to journalArticlepeer-review

Abstract

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAP DH) on the sporozoite surface and that GAP DH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAP DH. Therefore, Plasmodium-specific GAP DH epitopes may provide novel antigens for the development of a prehepatic vaccine.

Original languageEnglish (US)
Pages (from-to)2099-2112
Number of pages14
JournalJournal of Experimental Medicine
Volume213
Issue number10
DOIs
StatePublished - Sep 19 2016

ASJC Scopus subject areas

  • Medicine(all)

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