Antibodies against thrombospondin-related anonymous protein do not inhibit Plasmodium sporozoite infectivity in vivo

被引:86
作者
Gantt, S
Persson, C
Rose, K
Birkett, AJ
Abagyan, R
Nussenzweig, V
机构
[1] NYU, Sch Med, Dept Pathol, Michael Heidelberger Div Immunol, New York, NY 10016 USA
[2] NYU, Sch Med, Skirball Inst, New York, NY 10016 USA
[3] Univ Geneva, Ctr Med, Dept Med Biochem, CH-1211 Geneva 4, Switzerland
[4] Immune Complex Corp, San Diego, CA 92121 USA
关键词
D O I
10.1128/IAI.68.6.3667-3673.2000
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Thrombospondin-related anonymous protein (TRAP), a candidate malaria vaccine antigen, is required for Plasmodium sporozoite gliding motility and cell invasion. For the first time, the ability of antibodies against TRAP to inhibit sporozoite infectivity in vivo is evaluated in detail. TRAP contains an A-domain, a well-characterized adhesive motif found in integrins, We modeled here a three-dimensional structure of the TRAP A-domain of Plasmodium yoelii and located regions surrounding the MIDAS (metal ion-dependent adhesion site), the presumed business end of the domain. Mice were immunized,vith constructs containing these A-domain regions but were not protected from sporozoite challenge. Furthermore, monoclonal and rabbit polyclonal antibodies against the A-domain, the conserved N terminus, and the repeat region of TRAP had no effect on the gliding motility or sporozoite infectivity to mice. TRAP is located in micronemes, secretory organelles of apicomplexan parasites. Accordingly, the antibodies tested here stained cytoplasmic TRAP brightly by immunofluorescence. However, very little TRAP could be detected on the surface of sporozoites, In contrast, a dramatic relocalization of TR IP onto the parasite surface occurred when sporozoites were treated with calcium ionophore, This likely mimics the release of TRAP from micronemes when a sporozoite contacts its target cell in vivo. Contact with hepatoma cells in culture also appeared to induce the release of TRAP onto the surface of sporozoites, If large amounts of TRAP are released in close proximity to its cellular receptor(s), effective competitive inhibition by antibodies may be difficult to achieve.
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页码:3667 / 3673
页数:7
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