Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections
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PROVIDER: PRJNA761724 | ENA |
REPOSITORIES: ENA
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Project description:MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Herein, we observe that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provided protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogated the protection conferred by MV130 against Influenza A virus respiratory infection. MV130 induced reprogramming of mouse bone marrow progenitor cells and human monocytes, promoting an enhanced cytokine production that relied on metabolic and epigenetic shifts. Our results unveil that the mucosal a dministration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity. This SuperSeries is composed of the SubSeries listed below.
2021-11-10 | GSE183721 | GEO
Project description:MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.
| S-EPMC8755442 | biostudies-literature
Project description:Besides centrally induced innate immune memory/trained immunity in the bone marrow/peripheral blood by parenteral vaccination or infection, recently emerging evidence suggests that the barrier mucosal tissue-resident innate immune memory may develop via a local inflammatory pathway following mucosal immunologic exposure. However, it remains unclear whether the mucosal-resident innate immune memory may result from integrating distally generated immunological signals following parenteral vaccination/infection. We show here that subcutaneous Bacillus Calmette-Guérin (BCG) vaccination is able to induce memory alveolar macrophages (AM) and trained immunity at the respiratory barrier mucosa. Although parenteral BCG vaccine can centrally train bone marrow progenitors and circulating monocytes, induction of memory AM is entirely independent of circulating monocytes. Rather, parenteral BCG vaccination, via distal mycobacterial dissemination, causes a time-dependent alteration in gut microbiome, barrier function and microbial metabolites including short-chain fatty acids, and subsequently the changes in circulating and lung tissue metabolites, leading to induction of tissue-resident memory macrophages and trained innate immunity in the lung. Our study thus reveals a novel gut microbiota-mediated pathway for innate immune memory development at distal barrier mucosal tissues. Our findings have far-reaching implications in developing next-generation parenteral vaccine strategies against respiratory pathogens such as M.tb.
2022-09-16 | GSE213342 | GEO
Project description:Besides centrally induced innate immune memory/trained immunity in the bone marrow/peripheral blood by parenteral vaccination or infection, recently emerging evidence suggests that the barrier mucosal tissue-resident innate immune memory may develop via a local inflammatory pathway following mucosal immunologic exposure. However, it remains unclear whether the mucosal-resident innate immune memory may result from integrating distally generated immunological signals following parenteral vaccination/infection. We show here that subcutaneous Bacillus Calmette-Guérin (BCG) vaccination is able to induce memory alveolar macrophages (AM) and trained immunity at the respiratory barrier mucosa. Although parenteral BCG vaccine can centrally train bone marrow progenitors and circulating monocytes, induction of memory AM is entirely independent of circulating monocytes. Rather, parenteral BCG vaccination, via distal mycobacterial dissemination, causes a time-dependent alteration in gut microbiome, barrier function and microbial metabolites including short-chain fatty acids, and subsequently the changes in circulating and lung tissue metabolites, leading to induction of tissue-resident memory macrophages and trained innate immunity in the lung. Our study thus reveals a novel gut microbiota-mediated pathway for innate immune memory development at distal barrier mucosal tissues. Our findings have far-reaching implications in developing next-generation parenteral vaccine strategies against respiratory pathogens such as M.tb.
2022-09-16 | GSE213340 | GEO
Project description:We have developed a composite infection vaccine technology (ciVAX) assembled from approved products for rapid response to pandemics and biothreat agents. ciVAX consists of an injectable biomaterial scaffold containing factors that recruit, reprogram and release dendritic cells (DC) in vivo. For bacterial infections, ciVAX contains Fc-Mannose-Binding Lectin (FcMBL) microbeads with captured PAMPs fractions from inactivated bacterial cell-wall lysates. ciVAX vaccination generates potent humoral and T cell responses to bacterial antigens, and ciVAX protects mice and pigs against lethal E coli challenge in sepsis and septic shock models
2021-01-22 | MSV000086751 | MassIVE
Project description:The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. We performed transcriptomics analysis on 20 SARS-CoV-2 naïve individuals who received multiple doses of inactivated vaccine and five SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. These data help us understand the reaction mechanism of the host's molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.
2022-02-23 | GSE189263 | GEO
Project description:Trained immunity is classically characterized by long-term epigenetic reprogramming of innate immune cells to combat infectious diseases. Infection-induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic-organ injury remains largely unknown. Here, through establishing an in vivo β-glucan training and secondary LPS challenge-induced organ injury model in zebrafish larvae, we observe that induction of trained immunity could inhibit the pyroptosis of hepatocytes to alleviate septic-liver injury, with an elevated epigenetic modification of trimethylation at histone 3 lysine 4 (H3K4me3) that targets mitophagy activation. Moreover, we identify a novel C-type lectin domain receptor in zebrafish, named DrDectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring-mediated mitophagy activation and alleviating the pyroptosis-engaged septic-liver injury in vivo. Taken together, our results uncover a tissue-resident trained immunity in maintaining tissue homeostasis at a whole animal level, and offer a facile in vivo model to efficiently integrate trained immunity for immunotherapies.
2024-04-25 | GSE245156 | GEO
Project description:Antibiotic resistance and the pandemic of infectious diseases pose major hazards to human health. As a novel anti-infection strategy, trained immunity has a promising future. Recombinant Streptococcus pneumoniae Endopeptidase O (rPepO) is a novel trained immunity inducer that is a highly effective broad-spectrum anti-infective molecule. Here, we demonstrate that rPepO training induces a protective effect by improving the function of several immune cells. rPepO trains macrophages in the periphery to improve their immunological response. In addition, macrophage-derived complement C3 stimulates B lymphocytes to bolster the host's initial line of defense. While trained-macrophage-derived G-CSF changes the host's hematopoiesis and promotes central trained immunity. The "trained" label is found on freshly differentiated mononuclear macrophages, which also possess significantly enhanced anti-infective properties. Consequently, our research reveals that rPepO can induce peripheral and central trained immunity and possesses broad-spectrum and durable antimicrobial characteristics.
2023-12-31 | GSE222201 | GEO
Project description:The eradication of poliovirus from the majority of the world has been achieved through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at preventing paralytic poliomyelitis, however, they also have significant differences. Most importantly for this work is the risk of revertant virus from OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and others have previously described the use of an alphavirus-based adjuvant that can induce a mucosal immune response to a co-administered antigen even when delivered at a non-mucosal site. In this report, we describe the use of an alphavirus-based adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three poliovirus serotypes in mice even when administered intramuscularly. Furthermore, GVI3000 significantly increased the potency of IPV in rat potency tests as measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000 vaccine would reduce the dose of IPV needed and provide significantly improved mucosal immunity. This vaccine could be an effective tool to use in the poliovirus eradication campaign without risking the re-introduction of revertant poliovirus derived from OPV.
| S-EPMC3967568 | biostudies-literature
Project description:Respiratory viral infections reprogram pulmonary macrophages with altered anti-infectious functions. However, the potential function of virus-trained macrophages in antitumor immunity in the lung, a preferential target of both primary and metastatic malignancies, is not well understood. Using mouse models of influenza and lung metastatic tumors, we show here that influenza trains respiratory mucosal-resident alveolar macrophages (AMs) to exert long-lasting and tissue-specific antitumor immunity. Trained AMs infiltrate tumor lesions and have enhanced phagocytic and tumor cell cytotoxic functions, which are associated with epigenetic, transcriptional and metabolic resistance to tumor-induced immune suppression. Generation of antitumor trained immunity in AMs is dependent on interferon-γ and natural killer cells. Notably, human AMs with trained immunity traits in non-small cell lung cancer tissue are associated with a favorable immune microenvironment. These data reveal a function for trained resident macrophages in pulmonary mucosal antitumor immune surveillance. Induction of trained immunity in tissue-resident macrophages might thereby be a potential antitumor strategy.
2023-01-09 | GSE222149 | GEO