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

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Date
2020-05-26Author
Stoffel, Nicole U
Uyoga, Mary A
Mutuku, Francis M
Frost, Joe N
Mwasi, Edith
Paganini, Daniela
Van der klis, Fiona R. M
Malhotra, Indu J
LaBeaud, A. Desira´e
Ricci, Cristian
Karanja, Simon
Drakesmith, Hal
King, Charles H
Zimmermann, Michael B
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Show full item recordAbstract
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.
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. 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. 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.
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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
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