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Infection and Immunity, April 2003, p. 1833-1842, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1833-1842.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Repeat Sequences in Block 2 of Plasmodium falciparum Merozoite Surface Protein 1 Are Targets of Antibodies Associated with Protection from Malaria

Spencer D. Polley,1 Kevin K. A. Tetteh,1 David R. Cavanagh,2 Richard J. Pearce,1 Jennifer M. Lloyd,1 Kalifa A. Bojang,3 Daniel M. N. Okenu,4 Brian M. Greenwood,1 Jana S. McBride,2 and David J. Conway1*

London School of Hygiene and Tropical Medicine, London WC1E 7HT,1 Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom,2 MRC Laboratories, Fajara, The Gambia,3 Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria4

Received 30 October 2002/ Accepted 12 December 2002

Human antibodies to the block 2 region of Plasmodium falciparum merozoite surface protein 1 (MSP1) are associated with a reduced prospective risk of clinical malaria. Block 2 is highly polymorphic, but all known alleles can be grouped into three major types. Two of these types (the K1-like and MAD20-like types) contain type-specific sequences (found in all alleles of a particular type) that flank polymorphic tripeptide repeats. These repeats contain both type-specific and subtype-specific sequences. To evaluate the antibody recognition of these parts of block 2, a new panel of six recombinant proteins was used (fused type-specific flanking sequences and two representative repeat sequences for each of the K1-like and MAD20-like types separately). Extensive testing of these antigens and full-length block 2 antigens showed that human serum immunoglobulin G antibodies induced by infection can recognize (i) type-specific epitopes in the repeats, (ii) subtype-specific epitopes in the repeats, or (iii) type-specific epitopes in flanking sequences. A large prospective study in The Gambia showed that antibodies to the repeats are strongly associated with protection from clinical malaria. The results are important for design of a vaccine to induce protective antibodies, and they address hypotheses about repeat sequences in malaria antigens.

* Corresponding author. Mailing address: London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, United Kingdom. Phone: 20 7927 2331. Fax: 20 7636 8739. E-mail david.conway{at}lshtm.ac.uk.

Editor: S. H. E. Kaufmann

Infection and Immunity, April 2003, p. 1833-1842, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1833-1842.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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