Repeat sequences in block 2 of Plasmodium falciparum merozoite surface protein 1 are targets of antibodies associated with protection from malaria

S D Polley, K K A Tetteh, D R Cavanagh, R J Pearce, J M Lloyd, K A Bojang, D M N Okenu, B M Greenwood, J S McBride, D J Conway, David Cavanagh

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1833-1842
Number of pages10
JournalInfection and Immunity
Volume71
Issue number4
DOIs
Publication statusPublished - Apr 2003

Keywords

  • AOTUS MONKEYS
  • ANTIGEN GENE
  • T-CELL
  • PARASITE
  • RESPONSES
  • IMMUNE
  • EFFICACY
  • VACCINE
  • INFECTION
  • FRAGMENT

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