Identification of potential biomarkers of vaccine inflammation in mice
- Imperial College London, United Kingdom
- Max Planck Institute for Infection Biology, Germany
- Imperial College Healthcare NHS Trust, Hammersmith Hospital, United Kingdom
- GSK, United States
- GSK, Italy
Figures
Figure 1
Overview of the transcriptomic responses to the injected vaccines and TLR agonists in the injected muscle, the draining lymph nodes (MLN), and the blood.
The width of each violin is scaled to the number of genes that are differentially expressed at each given time point (BH-adjusted p-value <0.01). Differentially expressed genes were defined as those …
Figure 2 with 3 supplements
Gene-set enrichment analysis reveals distinct mechanisms of transcriptional response to the injected vaccines and TLR agonists.
Tissue data sets are presented as three coloured segments along the perimeter for the injected muscle (purple), the draining lymph nodes (green), and the blood compartment (red). An ordered list of …
Figure 2—figure supplement 1
Gene-set enrichment analysis in the muscle data set.
Enrichment scores were calculated for blood transcriptional modules defined by Li et al. (2014) using R package tmod (version 0.34) (US National Library of Medicine, 2004). The modules (in rows) are …
Figure 2—figure supplement 2
Gene-set enrichment analysis in the draining lymph nodes data set.
Enrichment scores were calculated for blood transcriptional modules defined by Li et al. (2014) using R package tmod (version 0.34) (US National Library of Medicine, 2004). The modules (in rows) are …
Figure 2—figure supplement 3
Gene-set enrichment analysis in blood data set.
Enrichment scores were calculated for blood transcriptional modules defined by Li et al. (2014) using R package tmod (version 0.34) (US National Library of Medicine, 2004). The modules (in rows) are …
Figure 3 with 1 supplement
Heatmap representing the transcript overlap between WGCNA modules and the reference modules.
Reference modules are the blood transcriptional modules defined by Li et al. (2014). These modules are shown in rows and are annotated within a higher functional group. Only WGCNA modules that …
Figure 3—figure supplement 1
Weighted gene co-expression network analysis of module–trait relationships.
Modules extracted by co-expression analyses in the injected muscle (A), draining lymph nodes (B), and blood (C) datasets are in rows labelled with a colour for each treatment and an identificaton …
Figure 4
Circular map representing the differentially expressed genes and reporting the observed correlations between each tissue.
The three tissues analysed are organised as in Figure 2 and are indicated on the outer part of the circular map. Each outer tile has a different colour to denote which injection they received: Fluad …
Figure 5 with 1 supplement
Serum chemokine and cytokine expression.
Serum chemokines and cytokines were measured using a Luminex bead 9-plex assay, and serum amyloid A3 was measured by quantitative ELISA. (A) Each panel shows the longitudinal expression of an individ…
Figure 5—figure supplement 1
Comparison of gene expression levels measured by microarray and protein levels of chemokines and cytokines measured by Luminex bead 9-plex assay and quantitative ELISA.
Differential expression of transcripts and proteins induced by the LPS immunisation are shown. Each panel shows the fold changes (transcripts – green line; proteins – orange line) of individual …
Figure 6
Comparison of gene expression levels measured by microarray with the protein levels of chemokines and cytokines measured by Luminex bead 9-plex assay and quantitative ELISA.
The correlations between fold changes in transcript and protein levels are presented in this heatmap. All measured chemokine and cytokines are in rows (left axis legend). Columns represent different …
Tables
Table 1
Vaccines and inflammatory agents.
The vaccines, TLR agonists, adjuvant and saline used in the present study are detailed. Vaccines were administered by injection of 1/10th the human dose in a 50 µL volume. TLR agonists, IFA and …
| Vaccine/TLR | Components | Abbreviation | Manufacturer |
|---|---|---|---|
| Pentavac SD | Diphtheria, tetanus, pertussis (whole cell), hepatitis B (rDNA) and haemophilus type b conjugate vaccine | Pentavac | Serum Institute India |
| Agrippal | Trivalent flu subunits – H3N2, H1N1 and influenza B | Tri-Flu | Seqirus |
| Fluad | Trivalent flu subunits – H3N2, H1N1 and influenza B + MF59 | Tri-Flu + MF59 | Seqirus |
| Engerix B | Recombinant hepatitis B sAg absorbed on alum | GlaxoSmithKline | |
| IFA | Montanide ISA 51 VG | Seppic | |
| LPS | LPS-EB Ultrapure | Invivogen | |
| Poly I:C | Polyinosinic:polycytidylic acid | Sigma |
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background) M. musculus, Female) | CB6F1/Crl; Strain Code 176 | Charles River | ||
| Commercial assay or kit | RNAprotect animal blood tubes | Qiagen | Cat number: 76544 | |
| Commercial assay or kit | miRNeasy mini kit | Qiagen | Cat number: 217004 | |
| Commercial assay or kit | QIAzol lysis reagent | Qiagen | Cat number: 79306 | |
| Commercial assay or kit | 9-plex Luminex | Bio-Techne | Cat number: LXSAMS-09 | |
| Chemical compound, drug | Pentavac SD | Serum Institute India | ||
| Chemical compound, drug | Agrippal | Seqirus | ||
| Chemical compound, drug | Fluad | Seqirus | ||
| Chemical compound, drug | Engerix B | GlaxoSmithKline | ||
| Chemical compound, drug | IFA - Montanide ISA 51 VG | Seppic | NSC#737063 | |
| Chemical compound, drug | LPS-EB Ultrapure | Invivogen | Cat number: tlrl-3pelps | |
| Chemical compound, drug | Poly I:C | Sigma | Cat number: P1530 |
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.46149.015
