The comparsion of gene expression in ALVAC- and Ad5-infected human monocyte-derived dendritic cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE103204 | GEO | 2017/09/27
SECONDARY ACCESSION(S): PRJNA400483
REPOSITORIES: GEO
Similar Datasets
Project description:We contrasted innate and adaptive immune responses of HIV vaccine candidates of varying efficacy in macaques that shared the ALVAC+gp120 protein boost with an ALVAC, DNA or Ad26 prime modality. The vaccine efficacies of the DNA/ALVAC+gp120 and ALVAC/ALVAC+gp120 vaccine regimens, both protective, were associated with qualitative temporal-spatial differences in the innate CD14+ and CD16+ cells in blood and tissues. The activation of hypoxia and the inflammasome in CD14+ DR+ CD16- classical monocytes and CD4+ Th2 responses correlated with a decreased risk of SIVmac251 acquisition. CD4+ Th2 cells, in turn, correlated with mucosal NKp44+ cells and mucosal protective antibodies to V2. In contrast, the Ad26/ALVAC+gp120 vaccine resulted in increased de novo differentiated CX3CR1+ CD163+ macrophages in lymph nodes, increased CD4+ Th17 cells in blood and rectal mucosa, and a lack vaccine efficacy. These data posit that the engagement of classical monocytes and inflammasome activation is central for the elicitation of protective innate and adaptive responses by the ALVAC-based HIV vaccine platform.
2018-02-23 | GSE108011 | GEO
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
Project description:We compare the immunogenicity of ALVAC- or NYVAC- based SIVmac251 vaccine regimens combined with gp120/alum boosts and their relative efficacy in a cohort of 65 female rhesus macaques. Both NYVAC- and ALVAC-based regimens induced equivalent titers of serum binding antibodies to gp120, whereas NYVAC elicited significantly higher envelope specific T cell responses. Surprisingly, however, only the ALVAC-based regimen was able to significantly decrease the risk of SIVmac251 acquisition following repeated low-dose intravaginal challenges. The risk of virus acquisition was associated negatively with the frequency of classical monocytes and positively with non-classical. The systems biology approach used to investigate the molecular basis of the different vaccine efficacies demonstrated specific expression profiles elicited by the ALVAC-based regimen that correlate with efficacy.
2020-03-05 | GSE138195 | GEO
Project description:Viral vectors are attractive vaccine platforms that elicit robust innate and adaptive immune responses; however, viral vector vaccine candidates vary greatly in their ability to induce protective immunity. Ad5 vectors elicit robust CD8+ T cell responses but typically characterized by an exhausted phenotype. The mechanisms by which Ad5 vectors induce dysfunctional CD8+ T cells have not been fully elucidated. Here we demonstrate that Ad5 vectors, but not Ad26 vectors, elicit exhausted antigen-specific IL-10+PD1+ CD4+ T cells with a dysfunctional transcriptional profile, and these cells effectively suppress CD8+ T cells responses in vivo. Induction of inhibitory CD4+ T cells by Ad5 vectors was associated with increased IL-27 expression, and IL-27 blockade improved CD4+ T cell polyfunctionality. Together our data highlight a novel role for IL-27 in regulating responses to viral vector vaccines.
2016-06-01 | GSE73118 | GEO
Project description:Viral vectors are attractive vaccine platforms that elicit robust innate and adaptive immune responses; however, viral vector vaccine candidates vary greatly in their ability to induce protective immunity. Ad5 vectors elicit robust CD8+ T cell responses but typically characterized by an exhausted phenotype. The mechanisms by which Ad5 vectors induce dysfunctional CD8+ T cells have not been fully elucidated. Here we demonstrate that Ad5 vectors, but not Ad26 vectors, elicit exhausted antigen-specific IL-10+PD1+ CD4+ T cells with a dysfunctional transcriptional profile, and these cells effectively suppress CD8+ T cells responses in vivo. Induction of inhibitory CD4+ T cells by Ad5 vectors was associated with increased IL-27 expression, and IL-27 blockade improved CD4+ T cell polyfunctionality. Together our data highlight a novel role for IL-27 in regulating responses to viral vector vaccines. Splenic CD45.2+ OT-II TCR-Tg CD4 T cells from CD45.1+ B6 mice immunized with Ad5-OVA or Ad26-OVA were purified by FACS on day 10 post-immunization
2016-06-01 | E-GEOD-73118 | biostudies-arrayexpress
Project description:The RV144 HIV vaccine trial remains the only study to demonstrate significant protection from future HIV-1 acquisition. One of the key components of the RV144 vaccine was the use of the canarypox vector ALVAC as the priming component. Since AIDSVAX, the booster component, alone failed to provide protection we hypothesized that the ALVAC prime contributed significantly to the generation of protection. To test this, we designed a NHP immunogenicity trial to mechanistically link ALVAC vaccination with the magnitude of V1V2 titers, the most significant immune correlate of reduced HIV-1 acquisition in RV144. Our objective was to use a systems biology approach to identify the transcription factors, target genes and immune pathways which were being induced by ALVAC vaccination and associated with higher V1V2 titers. We identified the transcription factor CREB1 and its target genes as rapidly induced by ALVAC in multiple immune subsets and that CREB1 drives the expression and activation of a network of other TFs which are critical for modulating immune responses. Pathways induced by this ALVAC-CREB1 axis include lymphocyte/leukocyte migration, lymphocyte differentiation, antigen processing and presentation, T cell co-stimulation and cytokine signaling.
2021-07-25 | GSE180748 | GEO
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
Project description:The Canarypox/gp120/Alum vaccines decreased the risk of HIV acquisition in humans. We demonstrate here the efficacy of this vaccine regimen also in the SIVmac251 macaque model when we used the alum but not the MF59 adjuvant. Analysis of innate and adaptive cell responses, envelope antibodies Fc profiles and glycoforms demonstrated a lower inflammatory response with alum than MF59. Alum elicited mucosal V2 peptide-specific IgG associated with vaccine efficacy whereas the MF59 induced mucosal V2 peptide-specific IgG associated with increased risk of infection. Alum modulated the expression of 12 genes, 7 of which are part of the RAS pathway, that correlates with vaccine efficacy and were linked to innate responses that preserve mucosal integrity and adaptive mucosal antibody response to V2. Thus, activation of the RAS pathway, preservation of mucosal integrity and mucosal antibody to V2 in concert, reduce the risk of SIVmac251 acquisition. Fifty-four (54) rhesus macaques were randomized into two vaccination groups. One group (n=27) was primed twice with ALVAC-SIV (at week 0 and week 4) and boosted twice with ALVAC-SIV/gp120 in MF59 adjuvant (at week 12 and week 24). The second group (n=27) was primed twice with ALVAC-SIV (at week 0 and week 4) and boosted twice with ALVAC-SIV/gp120 in Alum adjuvant (at week 12 and week 24). Blood samples were taken pre-vaccination, 24 hours after the first prime (post-1st imunization at week 0) and 24 hours after the first boost (post-3rd immunization at week 12). All the samples were taken before SIV challenge. Blood samples were conserved in PAXgene tubes. RNA was extracted and hybridized to Illumina beadchips. technical replicate: P162_P382_post1st, P162_P382_post1st_rep1
2016-05-29 | E-GEOD-72624 | biostudies-arrayexpress
Project description:The RV144 HIV vaccine trial remains the only study to demonstrate significant protection from future HIV-1 acquisition. One of the key components of the RV144 vaccine was the use of the canarypox vector ALVAC as the priming component. Since AIDSVAX, the booster component, alone failed to provide protection we hypothesized that the ALVAC prime contributed significantly to the generation of protection. To test this, we designed a NHP immunogenicity trial to mechanistically link ALVAC vaccination with the magnitude of V1V2 titers, the most significant immune correlate of reduced HIV-1 acquisition in RV144. Our objective was to use a systems biology approach to identify the transcription factors, target genes and immune pathways which were being induced by ALVAC vaccination and associated with higher V1V2 titers. We identified the transcription factor CREB1 and its target genes as rapidly induced by ALVAC in multiple immune subsets and that CREB1 drives the expression and activation of a network of other TFs which are critical for modulating immune responses. Pathways induced by this ALVAC-CREB1 axis include lymphocyte/leukocyte migration, lymphocyte differentiation, antigen processing and presentation, T cell co-stimulation and cytokine signaling.
2021-07-25 | GSE180747 | GEO
Project description:The RV144 HIV vaccine trial remains the only study to demonstrate significant protection from future HIV-1 acquisition. One of the key components of the RV144 vaccine was the use of the canarypox vector ALVAC as the priming component. Since AIDSVAX, the booster component, alone failed to provide protection we hypothesized that the ALVAC prime contributed significantly to the generation of protection. To test this, we designed a NHP immunogenicity trial to mechanistically link ALVAC vaccination with the magnitude of V1V2 titers, the most significant immune correlate of reduced HIV-1 acquisition in RV144. Our objective was to use a systems biology approach to identify the transcription factors, target genes and immune pathways which were being induced by ALVAC vaccination and associated with higher V1V2 titers. We identified the transcription factor CREB1 and its target genes as rapidly induced by ALVAC in multiple immune subsets and that CREB1 drives the expression and activation of a network of other TFs which are critical for modulating immune responses. Pathways induced by this ALVAC-CREB1 axis include lymphocyte/leukocyte migration, lymphocyte differentiation, antigen processing and presentation, T cell co-stimulation and cytokine signaling.
2021-07-26 | GSE180677 | GEO