Effects of Anaemia and Iron Supplementation on Vaccine Response: A Birth Cohort Study and a Randomized Trial Follow-Up Study in Kenyan Infants

Abstract

Objectives: Vaccines often underperform in low-income countries. Iron deficiency anaemia (IDA) may impair adaptive immunity and is common among African infants at time of vaccination. Our objective was to assess whether IDA impairs vaccine response and whether iron supplementation improves vaccine response. Methods: We performed two studies in southern Kenya. In study 1, we followed a birth cohort to age 18 mo and assessed whether IDA at time of vaccination with pentavalent, 10-valent pneumococcal and measles vaccines predicted vaccine response. Primary outcomes were serum IgG and seroconversion at age 24wk and 18 mo. Study 2 was a randomised trial cohort follow-up in children who received 5 mg iron daily or no iron for 4 mo starting at age 7.5 mo and received measles vaccine at 9 and 18 mo; primary outcomes were IgG, seroconversion and avidity assessed at 11.5 mo and 4.5y. Results: Study 1 ran from August 2013 to May 2017; 573 infants were enrolled and 303 completed the study. Controlling for sex, birthweight, anthropometrics and maternal antibodies, haemoglobin at time of vaccination was the strongest positive predictor of: (A) anti-diphtheria and anti-pertussis IgG at 24wk and 18 mo; (B) anti-pertussis filamentous hemagglutinin IgG at 24wk; and (C) anti-pneumococcus-S19 IgG at 18 mo (for all, P < 0.05). IDA and serum transferrin receptor at vaccination were the strongest predictors of seroconversion against diphtheria and pneumococcus-S19 at 18 mo (P < 0.05 for all). Study 2 ran from October 2014 to March 2019; 155 infants were recruited, 127 and 88 were assessed at age 11.5 mo and 4.5y. Infants who received iron at time of measles vaccination had higher anti-measles IgG (P = 0.0415), seroconversion (P = 0.0531) and IgG avidity (P = 0.0425) at 11.5 mo. Conclusions: To our knowledge these are the first prospective data from Africa assessing the impact of IDA at vaccination on vaccine response. IDA at time of vaccination is associated with decreased response to diphtheria, pertussis and pneumococcal vaccines. Primary response to measles vaccine is increased by iron supplementation. Because anaemia is common in African infants and because the vaccine-preventable disease burden is high, if IDA reduces immunogenicity of childhood vaccines its prevention could have major benefits.