A Longitudinal Study of Type-Specific Antibody Responses to Plasmodium falciparum Merozoite Surface Protein-1 in an Area of Unstable Malaria in Sudan

• Published in: The Journal of immunology (1950) 1998-07, Vol.161 (1), p.347-359
• Main Authors: Cavanagh, David R, Elhassan, Ibrahim M, Roper, Cally, Robinson, V. Jane, Giha, Haider, Holder, Anthony A, Hviid, Lars, Theander, Thor G, Arnot, David E, McBride, Jana S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Animals; Antibodies, Protozoan - biosynthesis; Antibodies, Protozoan - blood; Antibody Specificity; Antigenic Variation - genetics; Antigenic Variation - immunology; Conserved Sequence; Female; Genotype; Humans; Longitudinal Studies; Malaria, Falciparum - epidemiology; Malaria, Falciparum - immunology; Malaria, Falciparum - parasitology; Male; Merozoite Surface Protein 1; Molecular Sequence Data; Plasmodium falciparum - genetics; Plasmodium falciparum - immunology; Plasmodium falciparum - isolation & purification; Polymorphism, Genetic; Protein Precursors - immunology; Protozoan Proteins - immunology; Sudan - epidemiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.1.347

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.