Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response

Danielle I Stanisic, Freya Fowkes, Melanie Koinari, Sarah Javati, Enmoore Lin, Benson Kiniboro, Jack S Richards, Leanne J Robinson, Louis D Schofield, James W Kazura, Christopher L King, Peter Zimmerman, Ingrid Felger, Peter M Siba, Ivo Mueller, James G Beeson

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Abstract

Individuals in areas of Plasmodium falciparum endemicity develop immunity to malaria after repeated exposure. Knowledge of the acquisition and nature of protective immune responses to P. falciparum is presently limited, particularly for young children. We examined antibodies (IgM, IgG, and IgG subclasses) to merozoite antigens and their relationship to the prospective risk of malaria in children 1 to 4 years of age in a region of malaria endemicity in Papua New Guinea. IgG, IgG1, and IgG3 responses generally increased with age, were higher in children with active infection, and reflected geographic heterogeneity in malaria transmission. Antigenic properties, rather than host factors, appeared to be the main determinant of the type of IgG subclass produced. High antibody levels were not associated with protection from malaria; in contrast, they were typically associated with an increased risk of malaria. Adjustment for malaria exposure, using a novel molecular measure of the force of infection by P. falciparum, accounted for much of the increased risk, suggesting that the antibodies were markers of higher exposure to P. falciparum. Comparisons between antibodies in this cohort of young children and in a longitudinal cohort of older children suggested that the lack of protective association was explained by lower antibody levels among young children and that there is a threshold level of antibodies required for protection from malaria. Our results suggest that in populations with low immunity, such as young children, antibodies to merozoite antigens may act as biomarkers of malaria exposure and that, with increasing exposure and responses of higher magnitude, antibodies may act as biomarkers of protective immunity.
Original languageEnglish
Pages (from-to)646 - 660
Number of pages15
JournalInfection and Immunity
Volume83
Issue number2
DOIs
Publication statusPublished - 2015

Cite this

Stanisic, Danielle I ; Fowkes, Freya ; Koinari, Melanie ; Javati, Sarah ; Lin, Enmoore ; Kiniboro, Benson ; Richards, Jack S ; Robinson, Leanne J ; Schofield, Louis D ; Kazura, James W ; King, Christopher L ; Zimmerman, Peter ; Felger, Ingrid ; Siba, Peter M ; Mueller, Ivo ; Beeson, James G. / Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response. In: Infection and Immunity. 2015 ; Vol. 83, No. 2. pp. 646 - 660.
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abstract = "Individuals in areas of Plasmodium falciparum endemicity develop immunity to malaria after repeated exposure. Knowledge of the acquisition and nature of protective immune responses to P. falciparum is presently limited, particularly for young children. We examined antibodies (IgM, IgG, and IgG subclasses) to merozoite antigens and their relationship to the prospective risk of malaria in children 1 to 4 years of age in a region of malaria endemicity in Papua New Guinea. IgG, IgG1, and IgG3 responses generally increased with age, were higher in children with active infection, and reflected geographic heterogeneity in malaria transmission. Antigenic properties, rather than host factors, appeared to be the main determinant of the type of IgG subclass produced. High antibody levels were not associated with protection from malaria; in contrast, they were typically associated with an increased risk of malaria. Adjustment for malaria exposure, using a novel molecular measure of the force of infection by P. falciparum, accounted for much of the increased risk, suggesting that the antibodies were markers of higher exposure to P. falciparum. Comparisons between antibodies in this cohort of young children and in a longitudinal cohort of older children suggested that the lack of protective association was explained by lower antibody levels among young children and that there is a threshold level of antibodies required for protection from malaria. Our results suggest that in populations with low immunity, such as young children, antibodies to merozoite antigens may act as biomarkers of malaria exposure and that, with increasing exposure and responses of higher magnitude, antibodies may act as biomarkers of protective immunity.",
author = "Stanisic, {Danielle I} and Freya Fowkes and Melanie Koinari and Sarah Javati and Enmoore Lin and Benson Kiniboro and Richards, {Jack S} and Robinson, {Leanne J} and Schofield, {Louis D} and Kazura, {James W} and King, {Christopher L} and Peter Zimmerman and Ingrid Felger and Siba, {Peter M} and Ivo Mueller and Beeson, {James G}",
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Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response. / Stanisic, Danielle I; Fowkes, Freya; Koinari, Melanie; Javati, Sarah; Lin, Enmoore; Kiniboro, Benson; Richards, Jack S; Robinson, Leanne J; Schofield, Louis D; Kazura, James W; King, Christopher L; Zimmerman, Peter; Felger, Ingrid; Siba, Peter M; Mueller, Ivo; Beeson, James G.

In: Infection and Immunity, Vol. 83, No. 2, 2015, p. 646 - 660.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response

AU - Stanisic, Danielle I

AU - Fowkes, Freya

AU - Koinari, Melanie

AU - Javati, Sarah

AU - Lin, Enmoore

AU - Kiniboro, Benson

AU - Richards, Jack S

AU - Robinson, Leanne J

AU - Schofield, Louis D

AU - Kazura, James W

AU - King, Christopher L

AU - Zimmerman, Peter

AU - Felger, Ingrid

AU - Siba, Peter M

AU - Mueller, Ivo

AU - Beeson, James G

PY - 2015

Y1 - 2015

N2 - Individuals in areas of Plasmodium falciparum endemicity develop immunity to malaria after repeated exposure. Knowledge of the acquisition and nature of protective immune responses to P. falciparum is presently limited, particularly for young children. We examined antibodies (IgM, IgG, and IgG subclasses) to merozoite antigens and their relationship to the prospective risk of malaria in children 1 to 4 years of age in a region of malaria endemicity in Papua New Guinea. IgG, IgG1, and IgG3 responses generally increased with age, were higher in children with active infection, and reflected geographic heterogeneity in malaria transmission. Antigenic properties, rather than host factors, appeared to be the main determinant of the type of IgG subclass produced. High antibody levels were not associated with protection from malaria; in contrast, they were typically associated with an increased risk of malaria. Adjustment for malaria exposure, using a novel molecular measure of the force of infection by P. falciparum, accounted for much of the increased risk, suggesting that the antibodies were markers of higher exposure to P. falciparum. Comparisons between antibodies in this cohort of young children and in a longitudinal cohort of older children suggested that the lack of protective association was explained by lower antibody levels among young children and that there is a threshold level of antibodies required for protection from malaria. Our results suggest that in populations with low immunity, such as young children, antibodies to merozoite antigens may act as biomarkers of malaria exposure and that, with increasing exposure and responses of higher magnitude, antibodies may act as biomarkers of protective immunity.

AB - Individuals in areas of Plasmodium falciparum endemicity develop immunity to malaria after repeated exposure. Knowledge of the acquisition and nature of protective immune responses to P. falciparum is presently limited, particularly for young children. We examined antibodies (IgM, IgG, and IgG subclasses) to merozoite antigens and their relationship to the prospective risk of malaria in children 1 to 4 years of age in a region of malaria endemicity in Papua New Guinea. IgG, IgG1, and IgG3 responses generally increased with age, were higher in children with active infection, and reflected geographic heterogeneity in malaria transmission. Antigenic properties, rather than host factors, appeared to be the main determinant of the type of IgG subclass produced. High antibody levels were not associated with protection from malaria; in contrast, they were typically associated with an increased risk of malaria. Adjustment for malaria exposure, using a novel molecular measure of the force of infection by P. falciparum, accounted for much of the increased risk, suggesting that the antibodies were markers of higher exposure to P. falciparum. Comparisons between antibodies in this cohort of young children and in a longitudinal cohort of older children suggested that the lack of protective association was explained by lower antibody levels among young children and that there is a threshold level of antibodies required for protection from malaria. Our results suggest that in populations with low immunity, such as young children, antibodies to merozoite antigens may act as biomarkers of malaria exposure and that, with increasing exposure and responses of higher magnitude, antibodies may act as biomarkers of protective immunity.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294228/pdf/zii646.pdf

U2 - 10.1128/IAI.02398-14

DO - 10.1128/IAI.02398-14

M3 - Article

VL - 83

SP - 646

EP - 660

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

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ER -