Efficient control of tumor progression by CD4 T cell epitope-based prime-boost therapeutic vaccination
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PROVIDER: PRJNA733193 | ENA |
REPOSITORIES: ENA
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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.
2019-02-19 | E-MTAB-7697 | biostudies-arrayexpress
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.
2013-10-30 | E-GEOD-51849 | biostudies-arrayexpress
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:We reported the differences of transcriptomic landscapes and clonal TCRs in CD4 and CD8 T cells among the control group, vaccination group and naïve group.
2023-09-30 | GSE175690 | GEO
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.
2023-03-08 | GSE207389 | GEO
Project description:Heterologous prime-boost strategies are of interest for HIV vaccine development. The order of prime-boost components could be important for the induction of T-cell responses. In this phase I/II multi-arm trial, three vaccine candidates were used as prime or boost: MVA HIV-B (coding for Gag, Pol, Nef); HIV LIPO-5 (5 lipopeptides from Gag, Pol, Nef); DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, Env gp160 clade B). Healthy volunteers (n=92) were randomized to four groups: 1) MVA at weeks (W) 0/8 + LIPO-5 at W20/28 (M/L); 2) LIPO-5 at W0/8 + MVA at W20/28 (L/M); 3) DNA at W0/4/12 + LIPO-5 at W20/28 (G/L); 4) DNA at W0/4/12 + MVA at W20/28 (G/M). Frequency of IFNγ-ELISpot responders at W30 was 33%, 43%, 0% and 74%, respectively. Only MVA-receiving groups were further analyzed. Gene expression profiles of 79 subjects at different timepoints were analyzed by Illumina Whole-Genome Gene Expression BeadChips. Significant whole blood gene expression changes were observed two weeks after the first MVA injection, regardless of its use as prime or boost. An MVA gene signature was identified, including 86 genes mainly related to cell cycle pathways. Three prime-boost strategies led to CD4+ and CD8+ T cell responses and to a whole blood gene expression signature primarily due to their MVA HIV-B component.
2022-04-15 | GSE196172 | GEO
Project description:Since the introduction of new generation pertussis vaccines, resurgence of pertussis is observed in many developed countries. Former whole-cell pertussis vaccines (wP) are able to protect against disease and transmission but have been replaced in several industrialized countries because of their reactogenicity and adverse effects. Current acellular pertussis vaccines (aP), made of purified proteins of Bordetella pertussis, are efficient at preventing disease but fail to induce long-term protection from infection. While the systemic and mucosal T cell immunity induced by the two types of vaccines has been well described, much less is known concerning B cell responses. Taking advantage of an inducible AID-Cre-EYFP fate-mapping mouse model, we sorted and analyzed by scRNAseq the transcriptomic profiles of memory B cells after a combination of prime:boost with the two classes of vaccines. B220+EYFP+GL7-PNA- memory B cells from the draining lymph nodes (dLNs) of tamoxifen-fed mice were FACS sorted 7 weeks after boost, alongside with B220+EYFP+GL7+PNA+ germinal center (GC) B cells and B220+GL7-PNA-EYFP-IgD+ naive B cells as a control population for the unsupervised clustering analysis. Single-cell mRNA sequencing was performed according to an adapted version of the SORT-seq protocol (Muraro et al., 2016, PMID: 27693023, with primers described in van den Brink et al. 2017), with cDNA libraries generation, sequencing and reads alignment performed at Single Cell Discoveries (Utrecht, Netherlands).
2022-09-12 | E-MTAB-12156 | biostudies-arrayexpress
Project description:CD4+ T cells are essential for sustaining CD8+ T cell responses during a chronic infection. The adoptive transfer of virus-specific CD4+ T cells has been shown to efficiently rescue exhausted CD8+ T cells. However, the question of whether endogenous virus-specific CD4+ T cell responses can be enhanced by certain vaccination strategies and subsequently reinvigorate exhausted CD8+ T cells remains unexplored. In this study, we developed a CD4+ T cell epitope-based heterologous prime-boost immunization strategy and examined the efficacy of this strategy using a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. We primed chronically LCMV-infected mice with a Listeria monocytogenes vector that expressed the LCMV glycoprotein-specific I-Ab-restricted CD4+ T cell epitope GP61-80 (LM-GP61) and subsequently boosted the primed mice with an influenza virus A (PR8 strain) vector that expressed the same CD4+ T cell epitope (IAV-GP61). This heterologous prime-boost vaccination strategy elicited strong anti-viral CD4+ T cell responses, which further improved both the quantity and quality of the virus-specific CD8+ T cells and led to better control of the viral loads. The combination of this strategy and the blockade of the programmed cell death-1 (PD-1) inhibitory pathway further enhanced the anti-viral CD8+ T cell responses and viral clearance. Thus, a heterologous prime-boost immunization that selectively induces virus-specific CD4+ T cell responses in conjunction with blockade of the inhibitory pathway may represent a promising therapeutic approach to treating patients with chronic viral infections.
| S-EPMC6203753 | biostudies-literature
Project description:Epitope-specific T cell responses after SARS-CoV-2 vaccination [scRNA_dextramer_mixed_time]
| PRJNA1089645 | ENA
Project description:Clonal expansion is a hallmark of adaptive immunity, and appears to be driven by high antigen-specific receptor avidity as shown by research using murine in vivo models. In humans, however, the functionality of antigen-specific T cell clonotypes that are recruited into primary and recall immune responses remains surprisingly elusive. In this regard, the vaccination program during the SARS-CoV-2 pandemic represented a unique research opportunity by provision of highly standardized cohorts of healthy human individuals receiving immunizations against a previously unseen antigen. Here, we analyzed 30 HLA-typed individuals before, short-term and long-term after three mRNA vaccinations against SARS-CoV-2. We performed an in-depth characterization of the magnitude, phenotype, clonal composition and functionality of antigen-specific CD8 T cell responses by ELISPOT, flow cytometry and single-cell RNA sequencing, including CITE seq of 130 surface antigens and 16 T cell epitope specificities. 89 T cell receptors (TCRs) covering three complete epitope-specific repertoires were re-expressed by CRISPR/Cas9-mediated orthotopic TCR replacement and tested for their avidity. TCR repertoires underwent continuous tailoring, with high TCR avidity being linked to both clonal persistence and expansion. However, epitope-specific repertoires also maintained diversity by concomitant contraction and new emergence of functional T cell clones over time. These data on the phenotype and clonal selection within human antigen-specific T cell responses instruct our understanding of human T cell biology and may guide the development of enhanced or novel vaccines.
2024-10-31 | GSE261967 | GEO