A longitudinal study of type-specific antibody responses to Plasmodium falciparum merozoite surface protein-1 in an area of unstable malaria in Sudan.
Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. Immunity to MSP-1 has been implicated in protection against infection in animal models. However, MSP-1 is a polymorphic protein and its immune recognition by humans following infection is not well understood. We have compared the immunogenicity of conserved and polymorphic regions of MSP-1, the specificity of Ab responses to a polymorphic region of the Ag, and the duration of these responses in Sudanese villagers intermittently exposed to P. falciparum infections. Recombinant Ags representing the conserved N terminus (Block 1), the conserved C terminus, and the three main types of the major polymorphic region (Block 2) of MSP-1 were used to determine the specificity and longitudinal patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were assessed before, during, and after malaria transmission seasons for 4 yr. Ags from the Block 1 region were rarely recognized by any donor. Responses to the C-terminal Ag occurred in the majority of acutely infected individuals and thus were a reliable indicator of recent clinical infection. Ags from the polymorphic Block 2 region of MSP-1 were recognized by many, although not all individuals after clinical malaria infections. Responses to Block 2 were type specific and correlated with PCR typing of parasites present at the time of infection. Responses to all of these Ags declined within a few months of drug treatment and parasite clearance, indicating that naturally induced human Ab responses to MSP-1 are short lived.
Cavanagh
D R
DR
Institute of Cell, Animal and Population Biology, Division of Biological Sciences, University of Edinburgh, Scotland, United Kingdom. cavanagh@srv0.bio.ed.ac.uk
Elhassan
I M
IM
Roper
C
C
Robinson
V J
VJ
Giha
H
H
Holder
A A
AA
Hviid
L
L
Theander
T G
TG
Arnot
D E
DE
McBride
J S
JS
D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000097:blood; D000918:Antibody Specificity; D000940:Antigenic Variation / Q000235:genetics / Q000276:immunology; D017124:Conserved Sequence; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008297:Male; D020066:Merozoite Surface Protein 1; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D011498:Protein Precursors / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013397:Sudan / Q000453:epidemiology
D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins