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J Infect Dis. 2012 Nov 15;206(10):1512-20. doi: 10.1093/infdis/jis546. Epub 2012 Sep 4.

High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.

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  • 1Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA.

Abstract

BACKGROUND:

The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection.

METHODS:

We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses.

RESULTS:

The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders.

CONCLUSION:

We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

PMID:
22949304
[PubMed - indexed for MEDLINE]
PMCID:
PMC3475634
Free PMC Article
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