Antibodies Against Merozoite Surface Protein (MSP)-119 Are a Major Component of the Invasion-inhibitory Response in Individuals Immune to Malaria

doi:10.1084/jem.193.12.1403

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'Donnell^b, Tania F. de Koning-Ward^a,b, Rachel A. Burt^b, Moses Bockarie^c, John C. Reeder^c, Alan F. Cowman^b, and Brendan S. Crabb^a,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

Correspondence to: Brendan S. Crabb, The Walter & Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, VIC 3050, Australia. Tel:61-3-9345-2555 Fax:61-3-9347-0852 E-mail:crabb{at}wehi.edu.au.

Antibodies that bind to antigens expressed on the merozoiteform of the malaria parasite can inhibit parasite growth bypreventing merozoite invasion of red blood cells. Inhibitoryantibodies are found in the sera of malaria-immune individuals,however, the specificity of those that are important to thisprocess is not known. In this paper, we have used allelic replacementto construct a Plasmodium falciparum parasite line that expressesthe complete COOH-terminal fragment of merozoite surface protein(MSP)-1₁₉ from the divergent rodent malaria P. chabaudi. Bycomparing this transfected line with parental parasites thatdiffer only in MSP-1₁₉, we show that antibodies specific forthis domain are a major component of the inhibitory responsein P. falciparum–immune humans and P. chabaudi–immunemice. In some individual human sera, MSP-1₁₉ antibodies dominatedthe inhibitory activity. The finding that antibodies to a smallregion of a single protein play a major role in this processhas important implications for malaria immunity and is stronglysupportive of further understanding and development of MSP-1₁₉–basedvaccines.

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

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