Inhibitory and neutral antibodies to Plasmodium falciparum MSP119 form ring structures with their antigen.
Blood-stage malaria vaccine candidates include surface proteins of the merozoite. Antibodies to these proteins may either block essential steps during invasion or render the merozoite susceptible to phagocytosis or complement-mediated degradation. Structural information on merozoite surface proteins complexed to antibodies provides crucial information for knowledge-based vaccine design. The major merozoite surface protein MSP1 is an abundant surface molecule in Plasmodium falciparum. Only a subset of antibodies against MSP119 inhibits invasion (inhibitory antibodies), whereas other antibodies binding to MSP119 have no effect on invasion (neutral antibodies). Here we report on the complex of MSP119 with both inhibitory monoclonal antibody 12.10 and neutral monoclonal antibody 2F10. The complexes were established using both whole IgG's and Fab fragments, and analysed by dynamic light scattering, electron microscopy and analytical ultra centrifugation. Specific ring structures were formed in the ternary complex with the two antibodies, providing direct evidence of non-overlapping epitopes on MSP119. Mutational studies also indicated that the epitopes of the inhibitory and neutral antibodies are spatially remote.
Dekker
Carien
C
Division of Parasitology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK. cdekker@nimr.mrc.ac.uk
Uthaipibull
Chairat
C
Calder
Lesley J
LJ
Lock
Matthew
M
Grainger
Munira
M
Morgan
William D
WD
Dodson
Guy G
GG
Holder
Anthony A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000913:Antibodies, Protozoan / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004252:DNA Mutational Analysis; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D014461:Ultracentrifugation
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000936:Antigen-Antibody Complex; D000953:Antigens, Protozoan; D000939:Epitopes; D020066:Merozoite Surface Protein 1