Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA243915 | ENA |
REPOSITORIES: ENA
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Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927 PBMC collected pre or 28 days post vaccinated, stimulated with either Ag85A peptides (20 samples) or media alone (60).
2014-06-11 | E-GEOD-56561 | biostudies-arrayexpress
Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927 Whole blood collected 1 day post-vaccination with MVA85A or Candin placebo (82 samples)
2014-06-11 | E-GEOD-56559 | biostudies-arrayexpress
Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927
2014-06-11 | GSE56559 | GEO
Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927
2014-06-11 | GSE56561 | GEO
Project description:Immune response to MVA85A or placebo in BCG-vaccinated South African infants at day 1 post-vaccination
| PRJNA243916 | ENA
Project description:To assess changes in immune gene expression following BCG vaccination in infants, 6 infant rhesus macaques were vaccinated with BCG at 2 weeks of age. Whole blood was collected at the time of BCG vaccination, and at 3 weeks post-BCG, in EDTA coated tubes. Peripheral blood mononuclear cells were collected by ficoll and RNA was extracted using Macherey Nagel nucleospin columns. RNA from both timepoints was then used for gene expression analysis using the Nanostring nCounter platform.
2020-04-17 | GSE129989 | GEO
Project description:A greater understanding of the relationships between a vaccine, the immune response it induces, and protection from disease would greatly facilitate vaccine development. Modified Vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis (TB) vaccine designed to enhance responses induced by Bacille Calmette-Guerin (BCG). Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A and peaks one week post-vaccination, however, the variability in response between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression following vaccination with MVA85A and understand how these are related to long-term immunogenicity. 24 volunteers were vaccinated with 10^8 pfu MVA85A. 12 volunteers were vaccinated intramuscularly and 12 intradermally. Volunteers were healthy and did not have HIV, HCV, HBV or latent or active tuberculosis. Blood for this study was taken on the day of vaccination, immediately prior to the vaccine being given (day 0), and 2 and 7 days post-vaccination. Volunteers with a prior BCG vaccination were vaccinated with 1x10^8 pfu MVA85A either intradermally (id) or intramuscularly (im). Blood was taken immediately prior to vaccination (day 0) and 2 and 7 days post-vaccination. PBMCs were separated and frozen down. PBMCs were then thawed and RNA was extracted directly for microarray analysis. Some arrays contain control samples: from volunteers, incubated with either media alone or antigen 85, MVA85A or MVA wild type. These samples were used separately.
2012-09-28 | E-GEOD-40719 | biostudies-arrayexpress
Project description:Cattle were vaccinated at week 0 with the live attenuated M. bovis BCG SSI vaccine strain; some animals remain as non-vaccinated controls. After eight weeks animals were challenged intranodally with 108 BCG Tokyo cfu. Lymph nodes were harvested at week 11 and bacterial load in lymph nodes evaluated. Some BCG vaccinates had bacterial loads similar to those found in non-vaccinated animals (not-protected) and some animals had lower bacterial loads (protected) than non-vaccinated animals. Immune responses to mycobacteria were monitored in vitro by stimulation of whole blood with medium, purified protein derivative from M. bovis (PPD-B) or live BCG Tokyo longitudinally. Blood samples from 6 BCG-protected, 6 BCG-not-protected and 6 not-vaccinated. Challenged cattle stimulated with mycobacterial antigens or not were used to prepare RNA for RNAseq analysis at weeks 0 (vaccination), 8 (challenge), 9, 10 and 11. The outcome of this project would help not only in the selection of vaccine candidates but would also inform on the formulation of novel vaccines/vaccination strategies.
2018-07-30 | GSE84867 | GEO
Project description:Induction of trained immunity by human Bacille-Calmette-Guérin (BCG) vaccination is implicated in the beneficial heterologous effects of the vaccine, but the underlying mechanisms remain elusive. We performed global transcriptome analysis of sorted progenitors from bone marrow before (D0) and 90 days after vaccination (D90). BCG vaccination induced transcriptomic myeloid priming of the hematopoietic stem and progenitor cell (HSPC) compartment marked by the upregulation of myeloid and granulocytic pathways alongside the induction of transcription factors connected to myeloid cell function, namely Hepatocyte Nuclear Factors (HNF). These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1-related SNP variants correlating with immune training and elevated serum levels of the HNF1 target gene SERPINA1. Taken together, we reveal a transcriptomic reprograming of HSPCs and peripheral monocytes as a trait of in vivo BCG-induced trained immunity.
2020-06-30 | GSE124219 | GEO
Project description:Induction of trained immunity by human Bacille-Calmette-Guérin (BCG) vaccination is implicated in the beneficial heterologous effects of the vaccine, but the underlying mechanisms remain elusive. We performed global transcriptome analysis of sorted progenitors from bone marrow before (D0) and 90 days after vaccination (D90). BCG vaccination induced transcriptomic myeloid priming of the hematopoietic stem and progenitor cell (HSPC) compartment marked by the upregulation of myeloid and granulocytic pathways alongside the induction of transcription factors connected to myeloid cell function, namely Hepatocyte Nuclear Factors (HNF). These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1-related SNP variants correlating with immune training and elevated serum levels of the HNF1 target gene SERPINA1. Taken together, we reveal a transcriptomic reprograming of HSPCs and peripheral monocytes as a trait of in vivo BCG-induced trained immunity.
2020-06-30 | GSE124218 | GEO