The genomic landscape of monocytes and CD4+ T cells after BCG vaccination in Malawian infants
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1216563 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR32151541_1.fastq.gz | Fastqsanger.gz | |||
| SRR32151541_2.fastq.gz | Fastqsanger.gz | |||
| SRR32151542_1.fastq.gz | Fastqsanger.gz | |||
| SRR32151542_2.fastq.gz | Fastqsanger.gz |
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Project description:The Bacille Calmette-Guérin (BCG) vaccine administration studies in human adults determined that BCG-mediated mechanisms of protection include epigenetic reprogramming of innate immune cells and heterologous T cell immunity. The current study aimed to confirm that BCG immunization similarly impacts the functionally distinct infant immune system. Towards this goal, we applied RNA sequencing to assess molecular changes in circulating monocytes and CD4+ T cells of Malawian infants prior to and 2 to 13 weeks after BCG immunization. We identified 168 differentially expressed genes (DEGs), 14 upregulated and 152 downregulated, in monocytes after BCG vaccination. The upregulated monocyte DEGs were enriched in genes associated with metabolic pathways, in particular glycolysis and lipid metabolism. In CD4 T cells, 322 DEGs (95 upregulated and 226 downregulated) were identified after BCG vaccination, and these DEGs were representative of activation, proliferation, differentiation, and cell survival. These findings are consistent with data reported in BCG vaccinated adults and contribute to the understanding of molecular changes in monocytes and CD4 T cells that may explain the improved capacity of the infant immune system to respond to pathogens after BCG vaccination.
2025-05-30 | GSE288201 | 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 Whole blood collected 1 day post-vaccination with MVA85A or Candin placebo (82 samples)
2014-06-11 | E-GEOD-56559 | biostudies-arrayexpress
Project description:Bacillus Calmette–Guérin (BCG) vaccination immediately after birth provides overall protection against immune disorders in healthy infants. However, for vulnerable infants such as preterm or low birth weights, delayed BCG vaccination is usually recommended. The mechanism underlying this clinical application remains obscure. Here we reported that BCG vaccination abrogated the transitory appearance of immunosuppressive myeloid cells in neonatal mice, that is myeloid-derived suppressor cells (MDSCs) represented as the important immunoprotection against inflammatory diseases in early life. A combination of single-cell transcriptome, metabolite profiling, and functional analysis revealed that the upregulation of mTOR/HIF1a signaling and the enhanced glycolysis explained the underlying mechanism. Consequently, BCG vaccination significantly exacerbated the severity of necrotizing enterocolitis (NEC), a common clinical emergency primarily affecting preterm or low birth weight infants. Adoptive transfer of MDSCs or pharmalogical inhibition of glycolysis or mTOR signaling efficiently relieved the severity of NEC upon BCG vaccination. These observations suggest that BCG may diminish the protective mechanism of myeloid cells and enhances the susceptibility of NEC in vulnerable neonates.
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Project description:Analysis of PBMC from 10 week old infants vaccinated with BCG at birth. During follow-up 26 infants developed tuberculosis (TB) (non-protected by BCG) and 20 infants did not develop TB despite documented exposure (protected by BCG). PBMC were stimulated with media only or reconstituted BCG for 4 and 12 hours. Results provide insight into the mechanisms behind the failure of BCG to protect against disease.
2014-06-30 | GSE20716 | 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 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
2014-06-11 | GSE56559 | GEO
Project description:Vaccination against tuberculosis by intradermal Bacillus Calmette-Guérin (BCG) injection saves many lives, supposedly by inducing adaptive immune memory in lymphocytes. Epidemiologically, BCG vaccination is also associated with reduced childhood mortality unrelated to TB, which is attributed to innate immune memory, also termed trained immunity. We recently demonstrated improved protection against tuberculosis infection in highly susceptible rhesus macaques by mucosal BCG vaccination, correlating with a unique local but no peripheral immune profile. Here, we investigated local and peripheral innate immune function after intradermal versus mucosal vaccination with M. bovis BCG or the live attenuated, M. tuberculosis-derived candidate, MTBVAC. The results demonstrate an augmented frequency of trained immunity in monocytes after respiratory mucosal administration of live attenuated mycobacterial vaccines compared to intradermal immunization, with MTBVAC being equally potent as BCG. These results provide further support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.
2021-01-27 | GSE159046 | GEO
Project description:The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Here, we investigated the BCG-specific gene expression changes induced in PBMCs and CD4 memory T cells by BCG in individuals pre- and 8m post vaccination. We also determined whether reactivity against a peptide pool defined in individuals with controlled latent TB infection (MTB300), and with peptides homologous to peptides found in BCG, was boosted following BCG vaccination.
2021-12-06 | GSE156422 | 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:Vaccination with Bacillus Calmette-Guérin (BCG) induces long-term innate immune memory, also called trained immunity, characterized by metabolic and epigenetic changes leading to enhanced responsiveness upon exposure to heterologous pathogens. BCG vaccination was also shown to reduce systemic inflammation. Thus, BCG counteracts two significant immunological changes associated with aging: impaired responsiveness and elevated systemic inflammation. However, if and how BCG impacts other aging-related processes in immune cells, such as telomere shortening, remains unexplored. In this study, we investigated the transcriptional impact of BCG training on telomere maintenance-related genes through RNA sequencing and determined average telomere length from whole blood via RT-qPCR before and three months after BCG vaccination in two independent human cohorts. Trained immunity response was measured by ex-vivo cytokine production induced by a heterologous stimulus three months after vaccination compared to baseline. In addition, we examined the effects of BCG on telomerase activation using an in vitro trained immunity model. In vitro BCG training upregulated processes related to telomere maintenance and telomerase localization. In vivo, we observed shorter telomeres three months after BCG vaccination in both studies. Interestingly, the induction of a trained immunity response by BCG was correlated to the change in telomere length: more telomere shortening was observed in trained immunity non-responder individuals, particularly in males. Higher testosterone concentrations before vaccination were linked to more telomere loss. In vitro, BCG training of human monocytes activated the telomerase enzyme, predominantly in females, an effect that was blocked by exogenous testosterone treatment. Overall, this study reports sex-specific long-term impacts of BCG vaccination on telomerase activity and telomere maintenance. These data add to the arguments that BCG vaccination impacts aging mechanisms, which warrants more investigation.
2025-07-28 | GSE300272 | GEO