Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Systems analysis of the Merck Ad5/HIV vaccine reveals robust induction of a core innate immune gene network: in vivo 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. We defined the global early immune response to MRKAd5/HIV by profiling the PBMC transcriptomes from seven Ad5Neg individuals pre- and post-vaccination in vivo. Since the Step Study results suggested a deleterious effect of pre-existing Ad5 nAb on vaccine immunogenicity, we examined the vaccine-induced transcriptional responses from two Ad5Med and one Ad5Low individual 50 total samples were analyzed. This includes 5 time points post vaccination with MRKAd5/HIV for 10 independent human subjects. The time points were 0hr, 6hrs, 24hrs, 72hrs, and 168hrs. Seven of the subjects did not have pre-existing neutralizing antibodies to the vaccine vector (Ad5Neg). One subject had low level pre-existing neutralizing antibodies to the vaccine vector (Ad5Low). Two subjects had moderate level pre-existing neutralizing antibodies to the vaccine vector (Ad5Low).

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Zak 

PROVIDER: E-GEOD-22768 | 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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