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.

Conclusion: Influenza A(H1N1)pnd09 vaccination during pregnancy up-regulates TGF-β1 and down-regulates key mediators of the protective immunity.