Iron Deficiency Anemia at Time of Vaccination Predicts Decreased Vaccine Response and Iron Supplementation at Time of Vaccination Increases Humoral Vaccine Response: A Birth Cohort Study and a Randomized Trial Follow-Up Study in Kenyan Infants

Frontiers in Immunology

Hal Drakesmith¹  Indu J. Malhotra²  Charles H. King²  Fiona R. M. van der Klis³  Francis M. Mutuku⁴  Nicole U. Stoffel⁵  Michael B. Zimmermann⁵  Daniela Paganini⁵  Mary A. Uyoga⁵  Simon Karanja⁶  A. Desiráe LaBeaud⁷  Joe N. Frost⁸  Cristian Ricci⁹  Edith Mwasi^1,10 

[1] 0Haematology Theme, NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom;Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States;Centre for Infectious Disease Control, National Institute for Public Health and Environment (RIVM), Bilthoven, Netherlands;Department of Environment and Health Sciences, Technical University Mombasa, Mombasa, Kenya;Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, Laboratory of Human Nutrition, ETH Zürich, Zurich, Switzerland;Department of Medical Epidemiology, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya;Division of Infectious Diseases, Department of Pediatrics, Lucille Packard Children's Hospital at Stanford School of Medicine, Stanford, CA, United States;MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom;Pediatric Epidemiology, Department of Pediatrics, Medical Faculty, Leipzig University, Leipzig, Germany;Pediatrics Department, Msambweni County Referral Hospital, Msambweni, Kenya;

关键词: iron deficiency;    anemia;    iron;    vaccine response;    seroconversion;    infancy;   

DOI  :  10.3389/fimmu.2020.01313

来源: DOAJ

【 摘 要 】

Background: Iron deficiency may impair adaptive immunity and is common among African infants at time of vaccination. Whether iron deficiency impairs vaccine response and whether iron supplementation improves humoral vaccine response is uncertain.Methods: We performed two studies in southern coastal Kenya. In a birth cohort study, we followed infants to age 18 mo and assessed whether anemia or iron deficiency at time of vaccination predicted vaccine response to three-valent oral polio, diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine, ten-valent pneumococcal-conjugate vaccine and measles vaccine. Primary outcomes were anti-vaccine-IgG and seroconversion at age 24 wk and 18 mo. In a randomized trial cohort follow-up, children received a micronutrient powder (MNP) with 5 mg iron daily or a MNP without iron for 4 mo starting at age 7.5 mo and received measles vaccine at 9 and 18 mo; primary outcomes were anti-measles IgG, seroconversion and avidity at age 11.5 mo and 4.5 y.Findings: In the birth cohort study, 573 infants were enrolled and 303 completed the study. Controlling for sex, birthweight, anthropometric indices and maternal antibodies, hemoglobin at time of vaccination was the strongest positive predictor of: (A) anti-diphtheria and anti-pertussis-IgG at 24 wk (p = 0.0071, p = 0.0339) and 18 mo (p = 0.0182, p = 0.0360); (B) anti-pertussis filamentous hemagglutinin-IgG at 24 wk (p = 0.0423); and (C) anti-pneumococcus 19 IgG at 18 mo (p = 0.0129). Anemia and serum transferrin receptor at time of vaccination were the strongest predictors of seroconversion against diphtheria (p = 0.0484, p = 0.0439) and pneumococcus 19 at 18 mo (p = 0.0199, p = 0.0327). In the randomized trial, 155 infants were recruited, 127 and 88 were assessed at age 11.5 mo and 4.5 y. Compared to infants that did not receive iron, those who received iron at time of vaccination had higher anti-measles-IgG (p = 0.0415), seroconversion (p = 0.0531) and IgG avidity (p = 0.0425) at 11.5 mo.Interpretation: In Kenyan infants, anemia and iron deficiency at time of vaccination predict decreased response to diphtheria, pertussis and pneumococcal vaccines. Primary response to measles vaccine may be increased by iron supplementation at time of vaccination. These findings argue that correction of iron deficiency during early infancy may improve vaccine response.

【 授权许可】

Unknown