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

• Type of Material: Article
• Authors: Elizabeth P. Schlaudecker, Cincinnati Children's Hospital and Medical Center; Mark C. Steinhoff, Cincinnati Children's Hospital and Medical Center; Saad B Omer, Emory University; Monica M. McNeal, Cincinnati Children's Hospital and Medical Center; Eliza Roy, International Centre for Diarrheal Disease Research; Shams E. Arifeen, International Centre for Diarrheal Disease Research; Caitlin N. Dodd, Cincinnati Children's Hospital and Medical Center; Rubhana Raqib, International Centre for Diarrheal Disease Research; Robert F Breiman, Emory University; K. Zaman, International Centre for Diarrheal Disease Research
• Language: English
• Date: 2013-08-14
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Schlaudecker et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0070867
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 8
• Start Page: e70867
• End Page: e70867
• Grant/Funding Information: This work was supported by the Bill and Melinda Gates Foundation; a cooperative agreement (HRN-A-0096-90006-00) with the United States Agency for International Development; the Department of Health and Human Services; the National Vaccine Program Office; Wyeth Pharmaceuticals; the Thrasher Research Fund; Aventis Pasteur; the International Centre for Diarrheal Disease Research; and the Bloomberg School of Public Health at Johns Hopkins University.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: VACCINE; Science & Technology; IMMUNE-SYSTEM; INFANTS; CHILDREN; WOMEN; Multidisciplinary Sciences; BREAST-MILK; Science & Technology - Other Topics; SERUM; MATERNAL IMMUNIZATION; MOTHERS
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

Abstract

Background: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; http://clinicaltrials.gov/ct2/show/NCT00142389). Methods and Findings: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 cont rols 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).Conclusions: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. Trial Registration: ClinicalTrials.gov NCT00142389.