TY - JOUR
T1 - High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination
AU - Haralambieva, Iana H.
AU - Oberg, Ann L.
AU - Dhiman, Neelam
AU - Ovsyannikova, Inna G.
AU - Kennedy, Richard B.
AU - Grill, Diane E.
AU - Jacobson, Robert M.
AU - Poland, Gregory A.
N1 - Funding Information:
Financial support. The project described was supported by the National Institutes of Health (grant AI 40065). Potential conflicts of interest. All authors: No reported conflicts.
PY - 2012/11/15
Y1 - 2012/11/15
N2 - 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-/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.
AB - 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-/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.
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U2 - 10.1093/infdis/jis546
DO - 10.1093/infdis/jis546
M3 - Article
C2 - 22949304
AN - SCOPUS:84867736570
SN - 0022-1899
VL - 206
SP - 1512
EP - 1520
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -