Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Profiling 20,077 genes in 25 vaccine recipients: U133 Plus 2.0, Custom CDF Version 9

ABSTRACT: The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. Keywords: time course This study is a combination of 2 separate YF-17D vaccination trials. Trial 1 has 15 subjects, and Trial 2 has 10 subjects. The two trials occurred 1 year apart and used different lots of the vaccine. Enrolled volunteers were healthy, aged 18 to 45, and signed a written informed consent form. Potential volunteers were excluded from participating in the study if they were pregnant, or if they had been vaccinated previously with YF-17D. Blood samples were taken pre-vaccinaion to serve as a reference point for each individual, and post-vaccination samples were taken a days 1, 3, 7, and 21 after YF-17D vaccination. All subjects received YF-17D. Blood samples for microarray analysis were collected either in blue and black topped citrate buffered cell preparation tubes (CPT). Following PMBC isolation from CPT, 2 x 106 cells were lysed in 1 ml of TRIzol and stored at -80?C (Cat# 15596-026; Invitrogen Life Technologies). After all time points were collected for a subject, the samples were thawed, and the RNA isolation proceeded according to the manufacturer’s protocol.

ORGANISM(S): Homo sapiens

SUBMITTER: Troy Querec

PROVIDER: E-GEOD-13485 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.

Querec Troy D TD Akondy Rama S RS Lee Eva K EK Cao Weiping W Nakaya Helder I HI Teuwen Dirk D Pirani Ali A Gernert Kim K Deng Jiusheng J Marzolf Bruz B Kennedy Kathleen K Wu Haiyan H Bennouna Soumaya S Oluoch Herold H Miller Joseph J Vencio Ricardo Z RZ Mulligan Mark M Aderem Alan A Ahmed Rafi R Pulendran Bali B

Nature immunology 20081123 1

A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orche ...[more]

PMID: 19029902

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Project description:The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed evaluation of safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a system biology approach to compare hematological, biochemical, transcriptomic, innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans, but with slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques (by Day 7 [D7]), but titers >10 were reached in both species by D14 post-vaccination and were not significantly different by D28 (PRNT50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; p = 0.821). Changes in neutrophils, NK cells, monocytes, T and B cell frequency were higher in cynomolgus macaques and persisted for four weeks versus less than two weeks in humans. Low levels of systemic inflammatory cytokines (IL-1Ra, IL-8, MIP-1α, IP-10, MCP-1 or VEGF) were detected in either or both species, but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3–D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques (28% [5/18]) but generally absent in humans (except one participant [5%; 1/20]). Importance: Cynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans, and suggest a key role for type I IFN.

Dataset Information

Profiling 20,077 genes in 25 vaccine recipients: U133 Plus 2.0, Custom CDF Version 9

Publications

Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.

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