Transcriptomics

Dataset Information

3

Merck Ad5/HIV induces broad innate immune activation that predicts CD8+ T-cell responses but is attenuated by preexisting Ad5 immunity.


ABSTRACT: This SuperSeries is composed of the following subset Series: GSE22768: Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vivo analysis GSE22769: Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vitro analysis To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity. Refer to individual Series

ORGANISM(S): Homo sapiens  

SUBMITTER: Daniel Edward Zak   Margaret J McElrath  Erica Andersen-Nissen  Daniel E Zak  Alan Aderem 

PROVIDER: E-GEOD-22822 | ArrayExpress | 2012-11-20

SECONDARY ACCESSION(S): GSE22822PRJNA127865

REPOSITORIES: GEO, ArrayExpress

Dataset's files

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E-GEOD-22822.idf.txt Idf
E-GEOD-22822.processed.1.zip Processed
E-GEOD-22822.raw.1.zip Raw
E-GEOD-22822.raw.2.zip Raw
E-GEOD-22822.raw.3.zip Raw
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Publications

Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

Zak Daniel E DE   Andersen-Nissen Erica E   Peterson Eric R ER   Sato Alicia A   Hamilton M Kristina MK   Borgerding Joleen J   Krishnamurty Akshay T AT   Chang Joanne T JT   Adams Devin J DJ   Hensley Tiffany R TR   Salter Alexander I AI   Morgan Cecilia A CA   Duerr Ann C AC   De Rosa Stephen C SC   Aderem Alan A   McElrath M Juliana MJ  

Proceedings of the National Academy of Sciences of the United States of America 20121114 50


To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alteratio  ...[more]

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