title: High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.
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.
  
  
  CONCLUSIONS
  We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.forename: Ann L
authors.initials: AL
authors.lastname: Oberg
authors.forename: Neelam
authors.initials: N
authors.lastname: Dhiman
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.forename: Diane E
authors.initials: DE
authors.lastname: Grill
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000097:blood; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012899:Smallpox / Q000517:prevention & control; D012900:Smallpox Vaccine / Q000276:immunology*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D012333:RNA, Messenger; D012900:Smallpox Vaccine