Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort

Author:

Dent Arlene E.12,Malhotra Indu1,Wang Xuelie3,Babineau Denise3,Yeo Kee Thai2,Anderson Timothy4,Kimmel Rhonda J.1,Angov Evelina5,Lanar David E.5,Narum David6,Dutta Sheetij5,Richards Jack7,Beeson James G.78,Crabb Brendan S.7,Cowman Alan F.9,Horii Toshihiro10,Muchiri Eric11,Mungai Peter L.111,King Christopher L.1,Kazura James W.1

Affiliation:

1. Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA

2. Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA

3. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA

4. School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

5. Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

6. Laboratory of Malaria Immunology and Vaccinology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA

7. Burnet Institute, Melbourne, Australia

8. Department of Microbiology, Monash University, Melbourne, Australia

9. Walter and Eliza Hall Institute of Medical Research, Parkville, Australia

10. Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan

11. Division of Vector Borne and Neglected Tropical Diseases, Ministry of Public Health and Sanitation, Nairobi, Kenya

Abstract

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy

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