title: Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort.
abstract: IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitized in utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk of P. falciparum infection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA arlene.dent@case.edu.
authors.forename: Arlene E
authors.initials: AE
authors.lastname: Dent
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Indu
authors.initials: I
authors.lastname: Malhotra
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xuelie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Babineau
authors.affiliation: Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
authors.forename: Kee Thai
authors.initials: KT
authors.lastname: Yeo
authors.affiliation: School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Anderson
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Rhonda J
authors.initials: RJ
authors.lastname: Kimmel
authors.affiliation: Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.affiliation: Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
authors.forename: David
authors.initials: D
authors.lastname: Narum
authors.affiliation: Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Burnet Institute, Melbourne, Australia.
authors.forename: Jack
authors.initials: J
authors.lastname: Richards
authors.affiliation: Burnet Institute, Melbourne, Australia Department of Microbiology, Monash University, Melbourne, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.affiliation: Burnet Institute, Melbourne, Australia.
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.affiliation: Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.affiliation: Division of Vector Borne and Neglected Tropical Diseases, Ministry of Public Health and Sanitation, Nairobi, Kenya.
authors.forename: Eric
authors.initials: E
authors.lastname: Muchiri
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA Division of Vector Borne and Neglected Tropical Diseases, Ministry of Public Health and Sanitation, Nairobi, Kenya.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Mungai
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
mesh_terms: D000367:Age Factors; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002675:Child, Preschool; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000453:epidemiology / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D012698:Serologic Tests
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins