Antibodies against merozoite surface protein (MSP)-1(19) are a major component of the invasion-inhibitory response in individuals immune to malaria.
Antibodies that bind to antigens expressed on the merozoite form of the malaria parasite can inhibit parasite growth by preventing merozoite invasion of red blood cells. Inhibitory antibodies are found in the sera of malaria-immune individuals, however, the specificity of those that are important to this process is not known. In this paper, we have used allelic replacement to construct a Plasmodium falciparum parasite line that expresses the complete COOH-terminal fragment of merozoite surface protein (MSP)-1(19) from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-1(19), we show that antibodies specific for this domain are a major component of the inhibitory response in P. falciparum-immune humans and P. chabaudi-immune mice. In some individual human sera, MSP-1(19) antibodies dominated the inhibitory activity. The finding that antibodies to a small region of a single protein play a major role in this process has important implications for malaria immunity and is strongly supportive of further understanding and development of MSP-1(19)-based vaccines.
O'Donnell
R A
RA
Department of Microbiology & Immunology and the Co-operative Research Centre for Vaccine Technology, University of Melbourne, VIC 3010, Australia.
de Koning-Ward
T F
TF
Burt
R A
RA
Bockarie
M
M
Reeder
J C
JC
Cowman
A F
AF
Crabb
B S
BS
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000918:Antibody Specificity; D002455:Cell Division; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000737:chemistry; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D021261:Parasitic Sensitivity Tests; D010446:Peptide Fragments / Q000276:immunology; D016788:Plasmodium chabaudi / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016415:Sequence Alignment; D014162:Transfection
D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor