A longitudinal study of type-specific antibody responses to Plasmodium falciparum merozoite surface protein-1 in an area of unstable malaria in Sudan

TY - JOUR

T1 - A longitudinal study of type-specific antibody responses to Plasmodium falciparum merozoite surface protein-1 in an area of unstable malaria in Sudan

AU - Cavanagh, D R

AU - Elhassan, I M

AU - Roper, C

AU - Robinson, V J

AU - Giha, H

AU - Holder, A A

AU - Hviid, L

AU - Theander, T G

AU - Arnot, D E

AU - McBride, J S

N1 - Keywords: Adolescent; Adult; Animals; Antibodies, Protozoan; Antibody Specificity; Antigenic Variation; Conserved Sequence; Female; Genotype; Humans; Longitudinal Studies; Malaria, Falciparum; Male; Merozoite Surface Protein 1; Molecular Sequence Data; Plasmodium falciparum; Polymorphism, Genetic; Protein Precursors; Protozoan Proteins; Sudan

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 9647243

SN - 0022-1767

VL - 161

SP - 347

EP - 359

JO - Journal of Immunology

JF - Journal of Immunology

IS - 1

ER -