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Murine HIV-gagP24 CD8 T cells: bone marrow vs Lymph node

ABSTRACT: Transcriptional profiling to examine differences resulting from priming of virus-specific CD8 T cells in draining lymph node and in bone marrow, following intradermal injection of modified virus Ankara (MVA)-HIV gag. Transcriptional profiling of mouse pentamer H2kD-AMQMLKETI (HIV-gagP24) CD8 T cells from draining lymph nodes(LN) and bone marrow (BM ) 5 days following intradermal injection of MVA-HIV gag, and compared to naive (CD62L Hi CD44 int) CD8+ T cells from lymph node of naive mice (NTc).

ORGANISM(S): Mus musculus

PROVIDER: GSE41736 | GEO | 2012/10/23

SECONDARY ACCESSION(S): PRJNA178093

REPOSITORIES: GEO

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Murine HIV-gagP24 CD8 T cells: bone marrow vs Lymph node

Project description:Transcriptional profiling to examine differences resulting from priming of virus-specific CD8 T cells in draining lymph node and in bone marrow, following intradermal injection of modified virus Ankara (MVA)-HIV gag. Transcriptional profiling of mouse pentamer H2kD-AMQMLKETI (HIV-gagP24) CD8 T cells from draining lymph nodes(LN) and bone marrow (BM ) 5 days following intradermal injection of MVA-HIV gag, and compared to naive (CD62L Hi CD44 int) CD8+ T cells from lymph node of naive mice (NTc). Three-condition experiment, BM, LN and NTc. Experimental replicates: 5 BM, 5 LN, 5 NTc, RNA pooled from 3 independant experiments of 5 mice each.

2012-10-23 | E-GEOD-41736 | biostudies-arrayexpress

Genome-wide analysis of gene expression in lymph nodes and vaccination site in mice vaccinated with adenovirus and MVA mixed formulations

2012-12-01 | GSE30564 | GEO

Genome-wide analysis of gene expression in lymph nodes and vaccination site in mice vaccinated with adenovirus and MVA mixed formulations

Project description:Gene expression analysis in lymph nodes and site of injection (intradermal) after vaccination with adenovirus (Ad), modified vaccinia Ankara (MVA) or a mixed formulation of Ad+MVA. The hypothesis tested in the present study was that co-administration of two viral vectors induce a differential gene expression in the site of vaccination (dermis) and the draining lymph nodes that ultimately influences the protective ability of a vaccine against pre-erythrocytic malaria. Total RNA was isolated from the vaccination site (dermis) and lymph nodes after vaccination with adenovirus, MVA or Ad+MVA mixed co-administration after 6h and 24h (ear biopsies) and 9h, 24h and 72h for lymph nodes. Differential gene expression was assessed between vaccinated and non-immunized mice. Four ear biopsy samples did not pass quality control, and are not included in this submission.

2012-12-01 | E-GEOD-30564 | biostudies-arrayexpress

T-cell immunogenicity, gene expression profile and safety of four heterologous prime-boost combinations of HIV vaccine candidates in healthy volunteers – results of the randomized multi-arm phase I/II ANRS VRI01 trial

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.

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Seminal plasma exposures strengthen vaccine responses in the female reproductive tract mucosae

Project description:HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An effective HIV-1 vaccine should elicit mucosal immunity. However, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1+ SP intravaginal exposure on the local immune responses of nonhuman primates. Multiple HIV-1+ SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4+ T cells, which was not observed in the control group. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. The frequency and the quality of specific anti-MVA CD8+ T cell responses increased in the FRT exposed to SP. Furthermore SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c+ cells and CD8+ T cell recruitment in the FRT draining lymph nodes. CD11c+ cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections.

2019-02-12 | E-MTAB-7639 | biostudies-arrayexpress

Novel MVA Vector Expressing Anti-apoptotic gene, B13R, Delays Apoptosis and Enhances Humoral Responses

Project description:Modified vaccinia virus Ankara (MVA) has been explored as a vaccine vector for use against infectious diseases and cancer. MVA is an immunogenic, attenuated poxvirus capable of eliciting robust cellular and humoral responses in pre-clinical animal models and in patients. However, upon infection with MVA, cells undergo rapid apoptosis leading to faster clearance of recombinant antigens. The fragmentation of the anti-apoptotic gene B13R in MVA could contribute to this effect. Here, we replaced the fragmented B13R with a functional version and observed that MVA-B13R infected HeLa cells and muscle cell lines delayed caspase 3 activation compared to MVA indicating slower progression of apoptosis. For immunogenicity studies, mice were intramuscularly immunized with recombinant MVA or MVA-B13R expressing SIV Gag, Pol and HIV Env (SHIV). We observed higher Env-specific humoral responses from MVA-B13R SHIV compared to MVA SHIV mice. To determine differences in the innate immune response that may have contributed to the augmented humoral response, we performed RNA-Seq analysis on draining lymph node cells after immunization. Gene set enrichment analysis from day 1 after immunization showed that MVA-B13R SHIV immunizations were associated with a negative enrichment for type I and II interferon responses compared to MVA SHIV mice indicating MVA-B13R SHIV induces a delayed anti-viral interferon response that may lead to the enhanced humoral response observed. Taken together, these results demonstrate that restoring B13R functionality in MVA significantly delays MVA-induced apoptosis, augments Env-specific antibody responses, and is associated with reduced interferon-alpha and interferon-gamma responses induced after vaccination.

2018-11-27 | GSE119884 | GEO

Splenic memory CD8 T cell signature of enhanced responsiveness to vaccine boost

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

Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles

Project description:Dendritic cell subsets purified from skin-draining lymph nodes of C57BL/6J mice following intradermal injection of non-viable Nippostrongylus brasiliensis (Nb) or topical application of Dibutyl Phthalate-FITC. Results provide insight into the genetic programme induced in DC exposed to Th2 stimuli.

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Transcriptional landscape of CD8 T cell subsets

Project description:Transcriptional study of sorted CD8 Tcell subsets from LymphNode and Tumor Draining Lymph Node

2021-01-27 | GSE162179 | GEO

Expression data of muscle and draining lymph node after intramuscular ISCOM-Matrix vaccine adjuvant treatment

Project description:ISCOM vaccines induce a balanced Th1/Th2 response and cytotoxic T lymphocytes. The adjuvant component, ISCOM-Matrix, consists of purified saponin fractions, cholesterol and phospholipids. The mode of action for the ISCOM-Matrix is known to some extent but still we lack knowledge of important segments in initiation of the immune response. The study was performed to analyze the early transcriptional responses to the ISCOM-Matrix alone, without the use of co-administered antigen. Matrix M (AbISCOÂ® 100) was given as intramuscular injection and after 24 hours the pigs was sacrificed for gene expression analysis, performed for the injection site and the draining lymph node. Results revealed 594 and 362 genes to be differentially expressed (FC > 2; q < 0.05) at the injection site and in the lymph node, respectively. This show that the ISCOM-Matrix, without any antigen added, has a clear immunomodulatory effect at the site of administration as well as in the draining lymph node. Six pigs, castrated males, 11 weeks old was used for the experiment. They were sorted two weeks prior the treatment and kept separate throughout the experiment. 3 pigs were intramuscularly (biceps femoris) injected with ISCOM-Matrix (AbISCOÂ® 100) suspended in 1 ml sterile saline. 3 control animals were similarly injected with saline only. The pigs were sacrificed after 24 hours and muscle tissue from injection site and draining (internal iliac) lymph nodes were collected and transferred to RNAlater for RNA isolation.

2012-03-31 | E-GEOD-36306 | biostudies-arrayexpress

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