Interferon gene expression as marker of immune maturation and response to vaccination

Abstract

Abstract Background Interferons (IFN) play a major role in regulating innate and adaptive immune responses. Studies in adults and older children demonstrated significant correlations between IFN gene expression and antibody responses to influenza vaccines. However, there is still an incomplete understanding of the role of IFN in the ontogeny of the infant immune system and how they affect the immune response to vaccines in this population. Our objective with this study is to define longitudinal age-related changes in interferon gene expression and the changes induced by routine vaccinations. Methods We enrolled 2 cohorts of healthy children: 81 children aged < 2 years evaluated at one-time point to assess age-dependent changes in IFN gene expression; and 47 < 1 year olds evaluated at three times, before vaccination (day (d) 0) and d7 and d30 post-vaccination. Peripheral blood samples were collected to measure: (a) immune transcriptional profiles by microarrays; (b) immune cell populations by flow cytometry, and (c) antibody titers to PCV13, Hib and DTaP in the vaccination cohort. Results Analysis of first cohort demonstrated significant underexpression of IFN genes (n = 120) in infants aged <6 months compared with those 12–24 months. By 9 months IFN expression was similar to the older children. IFN gene expression correlated with the numbers of neutrophils and monocytes across all age groups. The second cohort was evaluated at three time points (d0, d7, and d30) during routine vaccinations at 2, 6, and 12 months. We compared transcriptional profiles post-vaccination with d0 for each group and observed consistent overexpression of IFN-related genes at d7 in the three age groups. In 2-month-old infants, we observed significant correlations between IFN genes (TAP1, IFIT1/2/3, OASL and GBP1) at d0 (before vaccination) and increase in antibody titers of the three vaccines analyzed (r = 0.5–0.7; P < 0.05). Among the top 15 genes who have the most significant correlations, eight are exclusively induced by type I IFN, six by type II IFN, and one is shared between the two types. Conclusion IFN gene expression at baseline is markedly reduced in infants <6 months. Routine vaccines were associated with marked increased in IFN gene expression at 2, 6, and 12 months. Baseline IFN expression at 2 months correlated with antibody responses to vaccines. Disclosures O. Ramilo, Abbvie: Board Member, Consulting fee; Regeneron: Board Member, Consulting fee; Janssen: Board Member and Investigator, Consulting fee and Research grant; NIH: Grant Investigator, Research grant