title: Prenatal malaria immune experience affects acquisition of Plasmodium falciparum merozoite surface protein-1 invasion inhibitory antibodies during infancy.
abstract: African infants are often born of mothers infected with malaria during pregnancy. This can result in fetal exposure to malaria-infected erythrocytes or their soluble products with subsequent fetal immune priming or tolerance in utero. We performed a cohort study of 30 newborns from a malaria holoendemic area of Kenya to determine whether T cell sensitization to Plasmodium falciparum merozoite surface protein-1 (MSP-1) at birth correlates with infant development of anti-MSP-1 Abs acquired as a consequence of natural malaria infection. Abs to the 42- and 19-kDa C-terminal processed fragments of MSP-1 were determined by serology and by a functional assay that quantifies invasion inhibition Abs against the MSP-1(19) merozoite ligand (MSP-1(19) IIA). Infants had detectable IgG and IgM Abs to MSP-1(42) and MSP-1(19) at 6 mo of age with no significant change by age 24-30 mo. In contrast, MSP-1(19) IIA levels increased from 6 to 24-30 mo of age (16-29%, p < 0.01). Infants with evidence of prenatal exposure to malaria (defined by P. falciparum detection in maternal, placental, and/or cord blood compartments) and T cell sensitization at birth (defined by cord blood lymphocyte cytokine responses to MSP-1) showed the greatest age-related increase in MSP-1(19) IIA compared with infants with prenatal exposure to malaria but who lacked detectable T cell MSP-1 sensitization. These data suggest that fetal sensitization or tolerance to MSP-1, associated with maternal malaria infection during pregnancy, affects the development of functional Ab responses to MSP-1 during infancy.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Arlene
authors.initials: A
authors.lastname: Dent
authors.forename: Indu
authors.initials: I
authors.lastname: Malhotra
authors.forename: Peter
authors.initials: P
authors.lastname: Mungai
authors.forename: Eric
authors.initials: E
authors.lastname: Muchiri
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology* / Q000469:parasitology; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000469:parasitology*; D011446:Prospective Studies
chemical_list: D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1