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Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vitro analysis

ABSTRACT: Here we applied a systems approach to define human innate immune signatures following MRKAd5/HIV immunization and to analyze the effects of pre-existing Ad5 immunity. To determine whether vaccine-induced changes could be ascribed to cell-intrinsic responses rather than cell population fluxes, fresh PBMC from independent Ad5Neg donors were stimulated in vitro with MRKAd5 vector lacking HIV-1 transgenes (MRKAd5). 22 total samples were analyzed. 14 of these are from in vivo vaccination of seven Ad5 seronegative subjects at two time points (0hr and 24hrs). 8 of these are from 24hr in vitro stimulation of PBMCs from four independent Ad5 seronegative donors with MRKAd5 empty vector or GTS buffer (Mock) at 20,000 viral particles per cell.

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Zak 

PROVIDER: E-GEOD-22769 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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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