Cited by 151Malaria Research and ControlHemoglobinopathies and Related DisordersBlood groups and transfusion

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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

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Stanisic, Danielle I., Fowkes, Freya J. I., Koinari, Melanie, Javati, Sarah, Lin, Enmoore, Kiniboro, Benson, Richards, Jack S., Robinson, Leanne J., Schofield, Louis, Kazura, James W., King, Christopher L., Zimmerman, Peter, Felger, Ingrid, Siba, Peter M., Mueller, Ivo, Beeson, James G.·2015·Infection and Immunity

DOI 10.1128/iai.02398-14PMC PMC4294228

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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.

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Authors: Stanisic, D. I., Fowkes, F. J. I., Koinari, M., Javati, S., Lin, E., Kiniboro, B., Richards, J. S., Robinson, L. J., Schofield, L., Kazura, J. W., King, C. L., Zimmerman, P., Felger, I., Siba, P. M., Mueller, I., & Beeson, J. G.
Affiliations: Griffith University (AU)
Burnet Institute (AU)
Papua New Guinea Institute of Medical Research (PG)
Walter and Eliza Hall Institute of Medical Research (AU)
Case Western Reserve University (US)
Swiss Tropical and Public Health Institute (CH)
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
ORCID: Stanisic, Danielle I.
Fowkes, Freya J. I.
Javati, Sarah
Lin, Enmoore
Richards, Jack S.
Robinson, Leanne J.
Kazura, James W.
Zimmerman, Peter
Felger, Ingrid
Siba, Peter M.
Beeson, James G.
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2015-02
Volume: 83
Issue: 2
Pages: 646-660
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.02398-14
PMC: PMC4294228
OpenAlex: W2127166169
Cited by: 151
References: 65
Citations by year: 2026: 7 · 2025: 11 · 2024: 8 · 2023: 12 · 2022: 11 · 2021: 19 · 2020: 16 · 2019: 18 · 2018: 11 · 2017: 15 · 2016: 12 · 2015: 11
FWCI: 12.61
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion, cc-by)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
ResearchOnline - JCU (James Cook University) (submittedVersion)
Griffith Research Online (submittedVersion)
Funders: National Institute of Allergy and Infectious Diseases (U19AI089686)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Health Sciences › Medicine › Hematology › Blood groups and transfusion
Keywords: Plasmodium falciparum, malaria immunity, merozoite antigens, antibody response, IgG subclasses, IgM, force of infection, malaria exposure, young children, protective immunity, biomarkers, age-related immune response, Papua New Guinea
MeSH terms: Age Factors, Antibodies, Protozoan, Antigens, Protozoan, Child, Preschool, Female, Humans, Immunoglobulin G, Immunoglobulin M, Infant, Male, Papua New Guinea, Plasmodium falciparum, Cohort Studies, Protozoan Proteins, Malaria, Falciparum, Merozoites

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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

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