Repeat sequences in block 2 of Plasmodium falciparum merozoite surface protein 1 are targets of antibodies associated with protection from malaria.
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.
Item Type | Article |
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Keywords | Adult, Amino Acid Sequence, Animal, Antibodies, Protozoan/*immunology, Antibody Specificity, Antigens, Protozoan/chemistry/genetics/immunology, Child, Child, Preschool, Human, 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, Support, Non-U.S. Gov't, Vaccination, Adult, Amino Acid Sequence, Animal, Antibodies, Protozoan, immunology, Antibody Specificity, Antigens, Protozoan, chemistry, genetics, immunology, Child, Child, Preschool, Human, 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, Support, Non-U.S. Gov't, Vaccination |
ISI | 181926200027 |
Explore Further
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC152097 (OA Location)
- 10.1128/IAI.71.4.1833-1842.2003 (DOI)
- 12654798 (PubMed)