IgA and Neutralizing Antibodies to Influenza A Virus in Human Milk: A Randomized Trial of Antenatal Influenza Immunization

<div><p>Background</p><p>Antenatal 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; <a href="http://clinicaltrials.gov/ct2/show/NCT00142389" target="_blank">http://clinicaltrials.gov/ct2/show/NCT00142389</a>).</p><p>Methods and Findings</p><p>The 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 (<i>p</i> = 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 (<i>p</i> = 0.0042) but not in infants of pneumococcal-vaccinated mothers (<i>p</i> = 0.4154).</p><p>Conclusions</p><p>The 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.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00142389" target="_blank">NCT00142389</a></p></div

CONSORT study diagram.

<p>Of the 340 women randomized to receive influenza vaccine or pneumococcal vaccine, breast milk samples from 57 women were analyzed for IgA antibody and neutralizing activity.</p

Breast milk IgA antibodies and influenza virus neutralization titers in influenza and control vaccines.

<p>Abbreviations: N, number; CI, confidence interval; GMC, geometric mean concentration.</p

Geometric mean neutralization titers in serum in influenza versus control vaccines.

<p>Geometric mean anti-influenza neutralization titers are significantly higher in the serum of influenza vaccinees compared to control vaccinees at delivery.</p

Geometric mean adjusted influenza-specific IgA in breast milk in influenza versus control vaccines.

<p>Geometric mean adjusted influenza-specific IgA antibody is significantly higher in the breast milk of influenza vaccinees compared to control vaccinees for at least 6 months postpartum.</p

Maternal and infant characteristics by vaccine group.

*<p>p values were calculated using a T test for all variables except Place of Delivery, Delivery Type, and Infant Sex (Chi Squared). ⁺ N = 14⁺⁺ N = 16.</p

GMCs of serum influenza specific IgA antibody and influenza virus neutralization titers in influenza and control vaccines.

<p>Abbreviations: N, number; CI, confidence interval; GMC, geometric mean concentration.</p