An mRNA-based universal vaccine candidate confers improved cross-protection against heterosubtypic influenza viruses in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE234756 | GEO | 2023/09/27
REPOSITORIES: GEO
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Project description:mRNA expression profiles of antigen-specific CD8+ T cells induced by DNA prime-DNA boost and DNA prime-VACV boost immunization regimen
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Project description:The generation of CD8+ T-cell memory is an important aim of immunization. While several distinct subsets of CD8+ T-cell memory have been described, the lineage relationships between effector (EFF), effector memory (EM) and central memory (CM) T cells remain contentious. Specifically, there is contradictory experimental evidence to support both the linear (Naive>EFF>EM>CM) and progressive differentiation (Naive>CM>EM>EFF) models. In this study, we applied a systems biology approach to examine global transcriptional relationships between the three major CD8+ T cell subsets arising endogenously as a result of vaccination with three different prime-boost vaccine regimens. Differential gene expression analysis and principle component analysis revealed that central memory cells were more closely related to naive T cells than both effector memory and effector cells. When the transcriptional relationships between subsets were enriched in an unbiased fashion with known global transcriptional changes that result when T-cells repeatedly encounter antigen, our analysis favored a model whereby cumulative antigenic stimulation drives differentiation specifically from Naive > CM > EM > EFF. These findings provide an insight into the lineage relationship between mature CD8+ T-cell subsets and will help in the rational design of vaccines aimed at generating effective immune responses against infections and cancer. Effector (EFF), effector memory (EM), central memory (CM) and naive CD8+ T cells from mice spleen. Memory subset arise endogenously as a result of vaccination with three different prime-boost vaccine regimens: DNA-rAd5, rAd5-rAd5 and rAd5-rLCMV.
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Project description:We addressed the question of primed CD8 T cell responsiveness to boost in a Balb/c mouse model of vaccination against gag of HIV-1, namely intramuscular (i.m.) prime with the Chimpanzee adenovector ChAd3-gag and i.m. boost with Modified Virus Ankara MVA-gag. In this setting, boost was more effective at day(d)100 than at d30 post-prime, as evaluated by multi-lymphoid organ assessment of gag-specific CD8 T cell frequency, CD62L-phenotype and in vivo killing activity at d45 post-boost. RNA-sequencing was used to compare memory signature of gag-specific spleen CD8 T cells at d100 post-prime with those at d30.
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Project description:Identifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most advanced malaria vaccine, has moderate efficacy in African children. In contrast, immunization with sporozoites under antimalarial chemoprophylaxis (CPS immunization) can provide 100% sterile protection in naïve adults. We used systems biology approaches to identify correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from subjects immunized with RTS,S/AS01E or chemo-attenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of subjects from two age cohorts and 3 African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve subjects participating in a CPS trial. We identified both pre-immunization and post-immunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and subjects from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-B, TLR, and monocyte-related signatures associated with protection. Pre-immunization signatures suggest the potential for strategies to prime the immune system before vaccination towards improving vaccine immunogenicity and efficacy. Finally, signatures of protection could be useful to determine efficacy in clinical trials, accelerating vaccine candidate testing. Nevertheless, signatures should be tested more extensively across multiple cohorts and trials to demonstrate their universal predictive capacity.
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Project description:In this study we attempt to elucidate some of the pathways involved in the immune response to vaccination and subsequent disease challenge using a transcriptomic approach. We exposed, via intra-peritoneal injection, three months old Asian seabass (Lates calcarifer) to a Streptococcus iniae vaccine. A control group was also set up where no vaccine was injected. Spleen and head kidney samples were collected at one and seven days post vaccination for transcriptomic analysis. At this point, there are four groups per organ: Day 1 vaccinated, Day 1 control, Day 7 vaccinated and Day 7 control. Subsequently, a pathogen challenge was carried out three weeks later and spleen and head kidneys were sampled at 25-29 hours post challenge for transcriptomic analysis. For control, mock challenged was carried out. At this point, there are four groups per organ: unvaccinated challenged, unvaccinated mock challenged, vaccinated challenged and vaccinated mock challenged. Total 57 samples. Spleen samples: At Day 1 and Day 7 post vaccination, 4 spleens were analyzed for each of the D1 control and D1 vaccinated groups and 3 spleens were analyzed for each of the D7 control and D7 vaccinated groups (total = 14 samples). At post pathogen challenge, 4 spleens were analyzed for each of these three groups - unvaccinated mock challenged, vaccinated challenged and vaccinated mock challenged and 3 spleens for the unvaccinated challenged group (total = 15 samples). Head Kidney samples: At Day 1 and Day 7 post vaccination, 3 head kidneys were analyzed for the control and vaccinated groups for both time points (total = 12 samples). At post pathogen challenge, 4 head kidneys were analyzed for each of the groups: unvaccinated challenged, unvaccinated mock challenged, vaccinated challenged and vaccinated mock challenged (total = 16 samples).
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Project description:Similar with others, our data proved that antigen-specific CD8+ T cells from mice primed with DNA and boosted by VACV were much more sensitive to antigen stimulation than those from DNA-boost. Since the mechanisms of in vivo tuning of antigen sensitivity (also termed functional avidity) is still not defined, we compared this two vaccination regimen at gene expression level. Results provide important information of which genes were selectively activated by VACV boost vaccination. For example, data shows that the expression levels of genes involved in Cancer and Wnt signaling pathways is more higher in DNA prime-VACV boost regimen that DNA prime-DNA boost vaccination.
2013-10-30 | GSE51849 | GEO
Project description: Not available
| S-EPMC7457018 | biostudies-literature
Project description:Similar with others, our data proved that antigen-specific CD8+ T cells from mice primed with DNA and boosted by VACV were much more sensitive to antigen stimulation than those from DNA-boost. Since the mechanisms of in vivo tuning of antigen sensitivity (also termed functional avidity) is still not defined, we compared this two vaccination regimen at gene expression level. Results provide important information of which genes were selectively activated by VACV boost vaccination. For example, data shows that the expression levels of genes involved in Cancer and Wnt signaling pathways is more higher in DNA prime-VACV boost regimen that DNA prime-DNA boost vaccination. To obtain sufficient of antigen-specific cells for microarray analysis, the OVA-specific CD8+ T cells from OT-1 mice were adoptively transferred into wild type mice and then immunized by DNA and VACV vaccine encoding OVA. Four week later, mice were scarificed and antigen-specific CD8+ T cells were emriched by CD45.1-PE antibody and anti-PE MicroBeads from splenocytes.Total RNA was extracted by the RNeasy Mini Kit (QIAGEN, Germany). Followed by amplification and biotin labeling, the samples were hybridized using Illumina Total Prep RNA Amplification Kit (Ambion, USA). Mouse WG-6v2 Expression BeadChips were used for analysis of transcriptome.
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