Mus musculus
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ABSTRACT:
PROVIDER: PRJNA350829 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression data from mouse organs after Advax injection Advax, an inulin-derived microparticle, has been developed as an adjuvant for several vaccines. Advax is a unique class of adjuvant which can potentiate the endogenous adjuvant effect of the vaccines through a not yet fully-identified, unique mechanisms of action.
2017-01-31 | GSE89249 | GEO
Project description:Vaccine adjuvants enhance adaptive immunity to co-administered antigens. Whereas the modes of action are multiple, the activation of antigen-presenting cells (APC) like dendritic cells by adjuvants is a prerequisite. Detection of microbial signals by innate sensors like Toll-like receptors (TLR) is a major mechanism of APC activation. Most candidate or licensed vaccines assume that adjuvant activity of TLR agonists depends on direct effect on APCs. This study addressed whether TLR stimulation of non-hematopoietic cells could contribute to the adjuvant effect. Nasal administration of flagellin enhanced T cell- and antibody-mediated immunity to co-administered antigens in a TLR5-dependent but inflammasome-independent manner. We found that lung radioresistant cells were sufficient to promote immunity, thereby suggesting that direct TLR5-mediated APC stimulation is dispensable to adjuvant activity. Consistent with this, radioresistant compartment is essential to stimulate the swift TLR5-dependent transcription. The transcriptional response was restricted to the epithelial compartment and was associated to the production of a narrow set of mediators including the chemokine CCL20, known to promote APC recruitment in mucosal tissues. Besides, flagellin was rapidly degraded in lower airways and was not transported into lung parenchyma or peripheral tissues. This study therefore suggests an unexpected mechanism for how TLR agonists act as adjuvant and how epithelium is instrumental to sense and integrate microbial signals to promote adaptive immunity. In conclusion, the immune-enhancing effect of adjuvants on epithelial cells can be harnessed for improving vaccines. 1 µg of flagellin was instillated intranasally to LPS-unresponsive C3H/HeJ mice. Total lung RNA was extracted 1h later and prepare for hybridization on Affymetrix microarrays.
2013-03-22 | E-GEOD-45369 | biostudies-arrayexpress
Project description:Vaccine adjuvants enhance adaptive immunity to co-administered antigens. Whereas the modes of action are multiple, the activation of antigen-presenting cells (APC) like dendritic cells by adjuvants is a prerequisite. Detection of microbial signals by innate sensors like Toll-like receptors (TLR) is a major mechanism of APC activation. Most candidate or licensed vaccines assume that adjuvant activity of TLR agonists depends on direct effect on APCs. This study addressed whether TLR stimulation of non-hematopoietic cells could contribute to the adjuvant effect. Nasal administration of flagellin enhanced T cell- and antibody-mediated immunity to co-administered antigens in a TLR5-dependent but inflammasome-independent manner. We found that lung radioresistant cells were sufficient to promote immunity, thereby suggesting that direct TLR5-mediated APC stimulation is dispensable to adjuvant activity. Consistent with this, radioresistant compartment is essential to stimulate the swift TLR5-dependent transcription. The transcriptional response was restricted to the epithelial compartment and was associated to the production of a narrow set of mediators including the chemokine CCL20, known to promote APC recruitment in mucosal tissues. Besides, flagellin was rapidly degraded in lower airways and was not transported into lung parenchyma or peripheral tissues. This study therefore suggests an unexpected mechanism for how TLR agonists act as adjuvant and how epithelium is instrumental to sense and integrate microbial signals to promote adaptive immunity. In conclusion, the immune-enhancing effect of adjuvants on epithelial cells can be harnessed for improving vaccines.
2013-03-22 | GSE45369 | GEO
Project description:The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines. 5 donors; 88 samples; duplicate technical replicates for the medium control for each donor for the BDCA1+ mDC population; single medium control for each donor for the BDCA3+ mDC population (15 total medium controls).
2014-10-22 | E-GEOD-56744 | biostudies-arrayexpress
Project description:The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines.
2014-10-22 | GSE56744 | GEO
Project description:The goal of this study was to identify the transcriptional mechanisms involved in the activation of the immune system by QS-21, a triterpene glycoside purified from the bark of Quillaja saponaria which has adjuvant activity in vivo. Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the Malaria and Zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T cell priming by QS-21 as revealed by the decrease in antigen-specific T cell response in Batf3−/− mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans
2016-12-06 | GSE90864 | GEO
Project description:Viral vectors are renowned for their inherent adjuvant effects. We here developed cancer vaccines based on the Vesicular Stomatitis Virus (VSV) vector using two different construction strategies.The first vaccine involved the traditional method of inserting tumor antigen genes into the VSV genome (SP vaccine). The second strategy, built upon the first, additionally displayed tumor antigens on the surface of the VSV, creating particulate antigen vaccine (CAD vaccine). To compare the early immune responses induced by these two vaccine strategies, we collected blood samples for RNA sequencing analysis at 24 hours post-immunization with both vaccines and a viral vector control group. The results indicated comparable early biological processes, including antiviral and innate immune responses, among the three groups. This confirms that the vector predominantly drives the early innate immune response.
2024-11-04 | GSE280660 | GEO
Project description:The induction of durable protective immune responses is the main goal of prophylactic vaccines, and adjuvants play an important role as drivers of such responses. Despite advances in vaccine strategies, a safe and effective HIV vaccine remains a significant challenge. The use of an appropriate adjuvant is crucial to the success of HIV vaccines. Here, we assessed the saponin/MPLA nanoparticle (SMNP) adjuvant with an HIV envelope (Env) trimer, evaluating the impact of adjuvant dose on the establishment of Env-specific memory B cell responses in non-human primates.
2025-03-11 | GSE291681 | GEO
Project description:Triple-negative breast cancer (TNBC) is an aggressive malignancy with high mortality and limited treatment options. While surgical resection removes the primary tumor, it often fails to prevent recurrence or metastasis, and despite the promise of immunotherapy, the response to immune checkpoint blockade remains poor. Here, we develop a cryogel-based dendritic cell (DC) vaccine that integrates gold nanodot-lipopolysaccharide (AuLPS)-loaded DCs, doxorubicin (Dox), and a PD-1 immune checkpoint blockade, effectively enhancing anti-tumor immunity in the post-surgical setting. The AuLPS nanoparticles (NPs) stabilize LPS assembly, optimizing Th1 adjuvant activity, thereby improving DC vaccine efficacy while minimizing adverse effects. The cryogel enables the sustained localized release of therapeutic agents at the surgical site, preserving DC viability, migration, and functionality within the tumor microenvironment. This strategy enhances DC activation and potentiates robust T-cell activation in both tumor-draining lymph nodes and tumor beds, leading to durable anti-tumor immunity. When administered at the post-surgical site in an orthotopic TNBC model, the aPD-1+Dox+AuLPS@DC cryogel vaccine significantly delays tumor recurrence, reduces distant metastases, and prolongs survival. These findings highlight cryogel-based DC vaccines as a promising post-surgical immunotherapy to overcome the limited response to immune checkpoint blockade and improve TNBC outcomes.
2025-02-17 | GSE289340 | GEO
Project description:Effective vaccines against viruses such as Influenza and SARS-CoV-2 must elicit a diverse repertoire of antibodies against multiple variant virus strains. However, antibody responses to current vaccines often lack cross-reactivity due to immunodominance. Here, we describe the synthesis of a toll-like receptor 7 agonist (TLR7)-nanoparticle adjuvant, TLR7-NP, constructed from TLR7 agonist-initiated ring-opening polymerization of lactide and self-assembly with poly(ethylene glycol)-b-poly(lactic-co-glycolic acid). TLR7-NP can enhance lymph node targeting, leading to persistent activation of immune cells. When mixed with Alum-adsorbed antigens, this TLR7-NP adjuvant elicited cross-reactive antibodies for both dominant and subdominant epitopes, as well as antigen-specific CD8+ T cell responses, in mice. TLR7-NP adjuvanted influenza subunit vaccine successfully protected mice from heterologous viral challenge. TLR7-NP also enhanced the antibody response to a SARS-CoV-2 subunit vaccine against multiple variants and revealed the mobilization of an antiviral response. We further demonstrate enhanced antigen-specific responses in human tonsil organoids with this novel adjuvant.
2022-11-14 | GSE217918 | GEO