Abstract
BackgroundAntenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389).Methods and FindingsThe Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154).ConclusionsThe sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the cellular and immunologic mechanisms of breast milk-mediated protection after antepartum immunization.Trial RegistrationClinicalTrials.gov NCT00142389
Highlights
Young infants (0–6 months of age) throughout the world experience high rates of influenza infection, clinic visits, and hospitalization [1,2,3,4,5,6]
Of 340 women enrolled in the study, 172 women received influenza vaccine and 168 received 23-valent pneumococcal capsular polysaccharide vaccine, of which 30 and 27, respectively, had both breast milk and serum available over 12 months for analysis
Differences were statistically significant for interval from vaccination to delivery, with mothers who received pneumococcal vaccine experiencing a 13 day longer interval than mothers who received influenza vaccine
Summary
Young infants (0–6 months of age) throughout the world experience high rates of influenza infection, clinic visits, and hospitalization [1,2,3,4,5,6]. Few studies have been done to assess the safety and immunogenicity of influenza immunization in infants before 6 months of age [7,8]. These studies suggest that influenza immunization in this age group produces low seroresponses, in part due to presence of passive maternal antibody [7,8]. We report the effect of antenatal immunization on the levels of specific antiinfluenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/ NCT00142389)
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