title: Age-dependent IgG subclass responses to Plasmodium falciparum EBA-175 are differentially associated with incidence of malaria in Mozambican children.
abstract: Plasmodium falciparum blood-stage antigens such as merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and the 175-kDa erythrocyte binding antigen (EBA-175) are considered important targets of naturally acquired immunity to malaria. However, it is not clear whether antibodies to these antigens are effectors in protection against clinical disease or mere markers of exposure. In the context of a randomized, placebo-controlled trial of intermittent preventive treatment in infants conducted between 2002 and 2004, antibody responses to Plasmodium falciparum blood-stage antigens in a cohort of 302 Mozambican children were evaluated by immunofluorescence antibody test and enzyme-linked immunosorbent assay at 5, 9, 12, and 24 months of age. We found that IgG subclass responses to EBA-175 were differentially associated with the incidence of malaria in the follow-up period. A double amount of cytophilic IgG1 or IgG3 was associated with a significant decrease in the incidence of malaria (incidence rate ratio [IRR] = 0.49, 95% confidence interval [CI] = 0.25 to 0.97, and P = 0.026 and IRR = 0.44, CI = 0.19 to 0.98, and P = 0.037, respectively), while a double amount of noncytophilic IgG4 was significantly correlated with an increased incidence of malaria (IRR = 3.07, CI = 1.08 to 8.78, P = 0.020). No significant associations between antibodies to the 19-kDa fragment of MSP-1 (MSP-1(19)) or AMA-1 and incidence of malaria were found. Age, previous episodes of malaria, present infection, and neighborhood of residence were the main factors influencing levels of antibodies to all merozoite antigens. Deeper understanding of the acquisition of antibodies against vaccine target antigens in early infancy is crucial for the rational development and deployment of malaria control tools in this vulnerable population.
authors.affiliation: Barcelona Centre for International Health Research, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. CDOBANO@clinic.ub.es
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
authors.forename: Diana
authors.initials: D
authors.lastname: Quelhas
authors.forename: Llorenç
authors.initials: L
authors.lastname: Quintó
authors.forename: Laura
authors.initials: L
authors.lastname: Puyol
authors.forename: Elisa
authors.initials: E
authors.lastname: Serra-Casas
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Tacilta
authors.initials: T
authors.lastname: Nhampossa
authors.forename: Eusebio
authors.initials: E
authors.lastname: Macete
authors.forename: Pedro
authors.initials: P
authors.lastname: Aide
authors.forename: Inacio
authors.initials: I
authors.lastname: Mandomando
authors.forename: Sergi
authors.initials: S
authors.lastname: Sanz
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Puniya
authors.forename: Bijender
authors.initials: B
authors.lastname: Singh
authors.forename: Puneet
authors.initials: P
authors.lastname: Gupta
authors.forename: Arindam
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Virander S
authors.initials: VS
authors.lastname: Chauhan
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.forename: Chetan E
authors.initials: CE
authors.lastname: Chitnis
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
mesh_terms: D000367:Age Factors; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D009073:Mozambique / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C065668:erythrocyte-binding antigen 175, Plasmodium