Splenic memory CD8 T cell signature of enhanced responsiveness to vaccine boost
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA854971 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19937256.fastq.gz | Fastqsanger.gz | |||
| SRR19937257.fastq.gz | Fastqsanger.gz | |||
| SRR19937258.fastq.gz | Fastqsanger.gz | |||
| SRR19937259.fastq.gz | Fastqsanger.gz | |||
| SRR19937260.fastq.gz | Fastqsanger.gz |
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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:A better understanding of innate responses induced by vaccination is critical for designing optimal vaccines. Here, we studied the diversity and dynamics of the NK cell compartment after prime-boost immunization with the modified vaccinia virus Ankara using cynomolgus macaques as a model. Mass cytometry was used to deeply characterize blood NK cells. The NK cell subphenotype composition was modified by the prime. Certain phenotypic changes induced by the prime were maintained over time and, as a result, the NK cell composition prior to boost differed from that before prime. The key phenotypic signature that distinguished NK cells responding to the boost from those responding to the prime included stronger expression of several cytotoxic, homing, and adhesion molecules, suggesting that NK cells at recall were functionally distinct. Our data reveal potential priming or imprinting of NK cells after the first vaccine injection. This study provides novel insights into prime-boost vaccination protocols that could be used to optimize future vaccines.
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Project description:The significant economic burden and high mortality rates resulting from seasonal influenza outbreaks, especially in high risk groups such as the elderly, represent an important public health problem. The prevailing inadequate efficacy of seasonal vaccines, both conventional and elderly-tailored, is a crucial bottleneck. Consequentially, understanding immunological and molecular mechanisms resulting in differential influenza vaccine responsiveness is a prerequisite for the development of new or improved vaccination strategies. To assess differences within the specific risk group of the elderly, randomly selected individuals (≥ 65 years) were immunized with the adjuvanted influenza vaccine Fluad®. Samples were subjected to transcriptome analysis. The analyses revealed profound features segregating vaccine responders from nonresponders as classified according to their vaccine-induced sero-conversion. Non-responders are characterized by a poorly functional, suppressive phenotype, showing a weaker humoral and cellular immune activation and more suppressive regulatory T and B cells. Triple responders display an efficient immune functionality characterized by the activation of humoral and cellular immunity and the up-regulation of genes related to signaling pathways, including those for anti-viral responses, protein processing and B cell activation. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness regardless of confounding age-dependent effects.
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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. 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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