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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).

ORGANISM(S): Homo sapiens

PROVIDER: GSE22769 | GEO | 2012/11/20

SECONDARY ACCESSION(S): PRJNA129111

REPOSITORIES: GEO

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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

Project description: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.

2012-11-20 | E-GEOD-22769 | biostudies-arrayexpress

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

2012-11-20 | GSE22768 | GEO

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

Project description: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).

2012-11-20 | E-GEOD-22768 | biostudies-arrayexpress

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

Project description: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

2012-11-20 | E-GEOD-22822 | biostudies-arrayexpress

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

Project description: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. This SuperSeries is composed of the SubSeries listed below.

2012-11-20 | GSE22822 | GEO

A Vaccine (Ad5.F35-hGCC-PADRE) for the Treatment of Gastrointestinal Adenocarcinoma

Project description:This phase IIA trial investigates the side effects of Ad5.F35-hGCC-PADRE vaccine and to see how well it works in treating patients with gastrointestinal adenocarcinoma. Ad5.F35-hGCC-PADRE vaccine may help to train the patient’s own immune system to identify and kill tumor cells and prevent it from coming back.

| 2317938 | ecrin-mdr-crc

Gene expression profiles of human Ad5- and CMV-specific CD4 T cells

2014-08-07 | GSE60180 | GEO

Gene expression profiles of human Ad5- and CMV-specific CD4 T cells

Project description:Analysis of global gene expression profiles of FACS-sorted, human Ad5- and CMV-specific CD4 T cells from the same PBMC sample of healthy donros, using affymetrix Human Gene 2.0ST Gene-Chips; The analysis show that Ad5- and CMV-specific CD4 T cells demonstrate differential gene expression profiles even though the cells are from the same PBMC PBMC from healthy donors (n=3) were CFSE-labeled, then equally divided and stimulated with Ad5 and CMV antigens; On day 6 post stimulation, Ag-specific CD4 T cells were sorted by flow based on CFSE-low.

2014-08-07 | E-GEOD-60180 | biostudies-arrayexpress

Effect of Ad5-porcine interferon-α pre-treatment in Ebola virus induced gene expression in pigs

Project description:Microarray analysis was done to compare the response of EBOV-infected pigs that were pre-treated with Ad5-porIFNα or PBS. At 3 days post EBOV infection, pigs that had been pre-treated with Ad5-porIFNα displayed upregulation of many genes related to the immune response in contrast to pigs treated with PBS. The largest category of induced genes included cytokines and chemokines that affect T-cell differentiation (IL27) and T-cell recruitment (CCL5, CCL23, CCL24, CXCL9, CXCL11)

2020-12-09 | GSE162846 | GEO

Innate immune signatures to a partially-efficacious HIV vaccine predict correlates of HIV-1 infection risk

Project description:Using specimens from a phase 1b trial of the RV144 regimen in HIV-1-uninfected South Africans (HVTN 097), we profiled innate responses to the first ALVAC-HIV immunization. PBMC transcriptional responses peaked 1 day post-vaccination. Type I and II interferon signaling pathways were activated, as were innate pathways critical for adaptive immune priming.

2021-03-17 | GSE164366 | GEO

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