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 journalArticle

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

  • Immunology and Allergy
  • Immunology

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