title: IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization.
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).
  
  
  RESULTS
  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 (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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00142389.
authors: Cincinnati Children's Hospital and Medical Center, Division of Infectious Diseases, Global Health Center, Cincinnati, Ohio, United States of America. Elizabeth.Schlaudecker@cchmc.org
authors: Elizabeth P
authors: EP
authors: Schlaudecker
authors: Mark C
authors: MC
authors: Steinhoff
authors: Saad B
authors: SB
authors: Omer
authors: Monica M
authors: MM
authors: McNeal
authors: Eliza
authors: E
authors: Roy
authors: Shams E
authors: SE
authors: Arifeen
authors: Caitlin N
authors: CN
authors: Dodd
authors: Rubhana
authors: R
authors: Raqib
authors: Robert F
authors: RF
authors: Breiman
authors: K
authors: K
authors: Zaman
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000032:analysis* / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D036861:Delivery, Obstetric; D005260:Female; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008297:Male; D008895:Milk, Human / Q000276:immunology*; D011247:Pregnancy; D013997:Time Factors; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D007070:Immunoglobulin A
references: Vaccine. 2011 Feb 1;29(6):1242-7
references: 21147127
references: N Engl J Med. 2006 Jul 6;355(1):31-40
references: 16822994
references: J Pediatr. 1992 Dec;121(6):852-6
references: 1447644
references: Pediatr Infect Dis J. 2012 Nov;31(11):1113-8
references: 22653487
references: J Infect Dis. 1995 Sep;172(3):723-8
references: 7658064
references: Am J Obstet Gynecol. 2011 Jun;204(6 Suppl 1):S141-8
references: 21492825
references: Am J Trop Med Hyg. 2008 Nov;79(5):787-92
references: 18981523
references: N Engl J Med. 2010 Apr 29;362(17):1644-6
references: 20427817
references: JAMA. 1980 Apr 4;243(13):1345-9
references: 6244421
references: Clin Infect Dis. 2011 Nov;53(9):885-92
references: 21946190
references: Acta Paediatr. 2010 Oct;99(10):1517-21
references: 20456265
references: Clin Infect Dis. 2010 Dec 15;51(12):1355-61
references: 21058908
references: Br J Exp Pathol. 1989 Apr;70(2):183-91
references: 2730839
references: Proc Nutr Soc. 2007 Aug;66(3):384-96
references: 17637091
references: Arch Pediatr Adolesc Med. 2011 Feb;165(2):104-11
references: 20921345
references: Pediatr Infect Dis J. 2009 Dec;28(12):1099-104
references: 19935270
references: Pediatr Infect Dis J. 1993 Aug;12(8):664-71
references: 8414780
references: Acta Paediatr. 1994 Jun;83(6):685
references: 7919776
references: Lancet. 1995 Nov 11;346(8985):1252-7
references: 7475716
references: J Pediatr. 2010 Feb;156(2 Suppl):S8-15
references: 20105666
references: Vaccine. 2002 May 22;20(17-18):2404-9
references: 12009297
references: Pediatr Infect Dis J. 2010 Mar;29(3):216-21
references: 20190613
references: J Infect Dis. 2008 May 15;197(10):1448-54
references: 18444800
references: J Clin Microbiol. 1999 Apr;37(4):937-43
references: 10074505
references: Pediatr Infect Dis J. 2011 Feb;30(2):170-3
references: 20856162
references: N Engl J Med. 2000 Jan 27;342(4):225-31
references: 10648763
references: Pediatrics. 2006 Feb;117(2):425-32
references: 16452362
references: N Engl J Med. 2008 Oct 9;359(15):1555-64
references: 18799552