TY - JOUR
T1 - Identification of GAP DH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion
AU - Cha, Sung Jae
AU - Kim, Min Sik
AU - Pandey, Akhilesh
AU - Jacobs-Lorena, Marcelo
N1 - Publisher Copyright:
© 2016 Cha et al.
PY - 2016/9/19
Y1 - 2016/9/19
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20160059
DO - 10.1084/jem.20160059
M3 - Article
C2 - 27551151
AN - SCOPUS:84992200627
SN - 0022-1007
VL - 213
SP - 2099
EP - 2112
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -