title: Airway mucosal immune-suppression in neonates of mothers receiving A(H1N1)pnd09 vaccination during pregnancy.
abstract: BACKGROUND
  It is recommended to vaccinate pregnant women against influenza. A possible impact on the immune expression of the fetus has never been studied. We aim to study the immune signature in the upper airways and the incidence of infections in neonates born to mothers receiving Influenza A(H1N1)pnd09 vaccination during pregnancy.
  
  
  METHODS
  One hundred and fifty-six women from the unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC2010) received Influenza A(H1N1)pnd09-vaccination during the 2009 pandemic. Fifty-one mothers received the vaccine during pregnancy and 105 after pregnancy; 332 neonates of nonvaccinated mothers were included as secondary controls. Nasal mucosal lining fluid was sampled in 488 neonates and assessed for interleukin (IL)-12p70, IP-10, interferon-gamma (IFN)-γ, tumor necrosis factor-alpha (TNF)-α, MIP-1β, MCP-1, MCP-4, IL-4, IL-5, IL-13, eotaxin-1, eotaxin-3, TARC, MDC, IL-17, IL-1β, IL-8, transforming growth factor beta (TGF)-β1, IL-10 and IL-2. Infections were monitored the first year of life by daily diary cards and clinical controls.
  
  
  RESULTS
  Neonates of mothers vaccinated during pregnancy had significant up-regulation of TGF-β1 [ratio = 1.52 (1.22-1.90), P = 0.0002], and corresponding down-regulation (P < 0.05) of IL-12p70, IFN-γ, IL-5, eotaxin-1, TARC, MDC, IL-8 in comparison to those vaccinated after pregnancy. The lag-time from vaccination during pregnancy to assessment of the immune signature showed significant and positive association to up-regulation of TGF-β1 levels (P = 0.0003) and significant negative association to other mediators. The study was not powered to study differences in the incidence of infections in early infancy which did not differ between the study groups.
  
  
  CONCLUSIONS
  Influenza A(H1N1)pnd09 vaccination during pregnancy up-regulates TGF-β1 and down-regulates key mediators of the protective immunity.
authors.affiliation: *From the Copenhagen Prospective Studies on Asthma in Childhood: COPSAC, Health Sciences, University of Copenhagen, Copenhagen University Hospital, Copenhagen; and †Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Bischoff
authors.forename: Nilofar V
authors.initials: NV
authors.lastname: Følsgaard
authors.forename: Nadja H
authors.initials: NH
authors.lastname: Vissing
authors.forename: Sune
authors.initials: S
authors.lastname: Birch
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D015331:Cohort Studies; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D009035:Mothers; D009297:Nasal Mucosa / Q000276:immunology; D011247:Pregnancy; D011446:Prospective Studies; D012137:Respiratory System / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000453:epidemiology*; D014611:Vaccination / Q000379:methods*
chemical_list: D016207:Cytokines; D007252:Influenza Vaccines