Airway Mucosal Immune-suppression in Neonates of Mothers Receiving A(H1N1)pnd09 Vaccination During P
Airway Mucosal Immune-suppression in Neonates of Mothers Receiving A(H1N1)pnd09 Vaccination During Pregnancy
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.
Conclusion Influenza A(H1N1)pnd09 vaccination during pregnancy up-regulates TGF-β1 and down-regulates key mediators of the protective immunity.
Influenza vaccination of pregnant women is generally recommended for the protection of both women and children, in particular during the recent Influenza A(H1N1)pnd09 (H1N1pnd09) pandemic in 2009.
The outcome of influenza infection is more severe during pregnancy, and even graver during influenza pandemics. Accordingly, the hospital admission and mortality rates were higher in pregnant women with influenza than in the general population during the 2009 pandemic, with increased rates of stillbirth, perinatal and neonatal mortality in infected pregnant women.
Influenza is also a major cause of morbidity and hospitalization in infants younger than 6 months. In particular the H1N1pnd09 pandemic caused more severe disease in the neonates and young infants than in older children, all unprotected from passive immunity to this novel virus.
No vaccination is approved for infants younger than 6 months. Therefore, influenza vaccination during pregnancy has been proposed as a safe way to protect infants, presumably by cocooning and from antibodies transmitted from the mother. Yet, the evidence is ambiguous as to the protective efficacy in the infants of vaccines given during pregnancy.
Influenza vaccination is generally considered safe for the pregnant mother and the fetus but there is no published evidence on the possible effect of vaccination during pregnancy on the neonatal immune status. Therefore, to examine the in vivo immune signature at the upper airways, we analyzed the undisturbed levels of cytokines and chemokines of the upper airway mucosa in neonates 4 weeks after birth and monitored the incidence of infections in the first year of life in infants of mothers receiving H1N1pnd09-vaccination during pregnancy versus neonates of mothers not vaccinated during pregnancy. Furthermore, we examined whether the time of vaccination during pregnancy impacted the cytokine and chemokine signature.
Abstract and Introduction
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.
Conclusion Influenza A(H1N1)pnd09 vaccination during pregnancy up-regulates TGF-β1 and down-regulates key mediators of the protective immunity.
Introduction
Influenza vaccination of pregnant women is generally recommended for the protection of both women and children, in particular during the recent Influenza A(H1N1)pnd09 (H1N1pnd09) pandemic in 2009.
The outcome of influenza infection is more severe during pregnancy, and even graver during influenza pandemics. Accordingly, the hospital admission and mortality rates were higher in pregnant women with influenza than in the general population during the 2009 pandemic, with increased rates of stillbirth, perinatal and neonatal mortality in infected pregnant women.
Influenza is also a major cause of morbidity and hospitalization in infants younger than 6 months. In particular the H1N1pnd09 pandemic caused more severe disease in the neonates and young infants than in older children, all unprotected from passive immunity to this novel virus.
No vaccination is approved for infants younger than 6 months. Therefore, influenza vaccination during pregnancy has been proposed as a safe way to protect infants, presumably by cocooning and from antibodies transmitted from the mother. Yet, the evidence is ambiguous as to the protective efficacy in the infants of vaccines given during pregnancy.
Influenza vaccination is generally considered safe for the pregnant mother and the fetus but there is no published evidence on the possible effect of vaccination during pregnancy on the neonatal immune status. Therefore, to examine the in vivo immune signature at the upper airways, we analyzed the undisturbed levels of cytokines and chemokines of the upper airway mucosa in neonates 4 weeks after birth and monitored the incidence of infections in the first year of life in infants of mothers receiving H1N1pnd09-vaccination during pregnancy versus neonates of mothers not vaccinated during pregnancy. Furthermore, we examined whether the time of vaccination during pregnancy impacted the cytokine and chemokine signature.
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