The Journal of Experimental Medicine
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Published online 18 June 2001.
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© The Rockefeller University Press, 0022-1007/2001/6/1403/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 12, June 18, 2001 1403-1412

Original Article

Antibodies against Merozoite Surface Protein (Msp)-119 Are a Major Component of the Invasion-Inhibitory Response in Individuals Immune to Malaria

Rebecca A. O'Donnellb, Tania F. de Koning-Warda,b, Rachel A. Burtb, Moses Bockariec, John C. Reederc, Alan F. Cowmanb, and Brendan S. Crabba,b

a Department of Microbiology & Immunology and the Co-operative Research Centre for Vaccine Technology, University of Melbourne, VIC 3010, Australia
b The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3050, Australia
c Papua New Guinea Institute of Medical Research, Goroka EHP 441 and Madang MAD 511, Papua New Guinea
The Walter & Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, VIC 3050, Australia.61-3-9347-085261-3-9345-2555

crabb{at}wehi.edu.au

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)-119 from the divergent rodent malaria P. chabaudi. By comparing this transfected line with parental parasites that differ only in MSP-119, 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-119 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-119–based vaccines.

Key Words: Plasmodium • merozoite • invasion • human sera • malaria

Abbreviations used in this paper: EGF, epidermal growth factor; GST, glutathione S transferase; HNIS, human nonimmune sera; IFA, immunofluorescence assay; MSP, merozoite surface protein; OD, optical density.

© 2001 The Rockefeller University Press


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