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

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.

• Authors: Spencer D Polley, Kevin K A Tetteh, David R Cavanagh, Richard J Pearce, Jennifer M Lloyd, Kalifa A Bojang, Daniel M N Okenu, Brian M Greenwood, Jana S McBride, David J Conway
• Journal: Infection and immunity (Infect Immun) Vol. 71 Issue 4 Pg. 1833-42 (Apr 2003) ISSN: 0019-9567 [Print] United States
• PMID: 12654798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Protozoan
• Antigens, Protozoan
• Immunoglobulin G
• Malaria Vaccines
• Merozoite Surface Protein 1

Topics

• Adult
• Amino Acid Sequence
• Animals
• Antibodies, Protozoan (immunology)
• Antibody Specificity
• Antigens, Protozoan (chemistry, genetics, immunology)
• Child
• Child, Preschool
• Humans
• Immunoglobulin G (immunology)
• Malaria Vaccines (administration & dosage, immunology)
• Malaria, Falciparum (immunology, prevention & control)
• Merozoite Surface Protein 1 (chemistry, genetics, immunology)
• Mice
• Mice, Inbred CBA
• Molecular Sequence Data
• Plasmodium falciparum (immunology)
• Repetitive Sequences, Nucleic Acid (immunology)
• Vaccination