Serum antibodies from malaria-exposed people recognize conserved epitopes formed by the two epidermal growth factor motifs of MSP1(19), the carboxy-terminal fragment of the major merozoite surface protein of Plasmodium falciparum.
The major merozoite surface protein of Plasmodium falciparum (PfMSP1) is a candidate antigen for a malaria vaccine. A 19-kDa C-terminal processing product of PfMSP1 (PfMSP1(19)) is composed of two domains sharing a cysteine-rich motif with epidermal growth factor (EGF) and is the target of monoclonal antibodies which block erythrocyte invasion in vitro. We have evaluated human antibody responses to PfMSP1(19) by using recombinant proteins representing the EGF motifs encoded by the two main alleles of the MSP1 gene. We find that both EGF motifs are antigenic but that only 10 to 20% of malaria-exposed individuals have serum antibodies that recognized either of the motifs. When both EGF motifs were expressed together as a single protein, they were recognized by more than 40% of sera from malaria-exposed individuals. Major epitopes recognized by human antibodies are dependent upon the correct tertiary structure of the protein and are cross-reactive between the different allelic sequences of PfMSP1(19). This suggests that antibodies induced by vaccination with one or the other allelic forms of the protein could recognize all strains of P. falciparum. Immunoglobulin G (IgG) subclass-specific enzyme immunoassays indicate that PfMSP1(19) antibodies are predominantly of the IgG1 subclass.
Egan
A F
AF
Institute of Cell, Animal and Population Biology, University of Edinburgh, United Kingdom.
Chappel
J A
JA
Burghaus
P A
PA
Morris
J S
JS
McBride
J S
JS
Holder
A A
AA
Kaslow
D C
DC
Riley
E M
EM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D016384:Consensus Sequence; D003429:Cross Reactions; D004220:Disulfides; D018604:Epitope Mapping; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology*; D020066:Merozoite Surface Protein 1; D008875:Middle Aged; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004220:Disulfides; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; D011994:Recombinant Proteins