Dataset Information

?-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs.

ABSTRACT: The mechanisms of trained immunity have been extensively described in vitro and the beneficial effects are starting to be deciphered in in vivo settings. Prototypical compounds inducing trained immunity, such as ?-glucans, act through epigenetic reprogramming and metabolic changes of innate immune cells. The recent advances in this field have opened new areas for the development of Trained immunity-based adjuvants (TIbAs). In this study, we assessed in dogs the potential immune training effects of ?-glucans as well as their capacity to enhance the adaptive immune response of an inactivated rabies vaccine (Rabisin®). Injection of ?-glucan from Euglena gracilis was performed 1 month before vaccination with Rabisin® supplemented or not with the same ?-glucan used as adjuvant. Trained innate immunity parameters were assessed during the first month of the trial. The second phase of the study was focused on the ability of ?-glucan to enhance adaptive immune responses measured by multiple immunological parameters. B and T-cell specific responses were monitored to evaluate the immunogenicity of the rabies vaccine adjuvanted with ?-glucan or not. Our preliminary results support that adjuvantation of Rabisin® vaccine with ?-glucan elicit a higher B-lymphocyte immune response, the prevailing factor of protection against rabies. ?-glucan also tend to stimulate the T cell response as shown by the cytokine secretion profile of PBMCs re-stimulated ex vivo. Our data are providing new insights on the impact of trained immunity on the adaptive immune response to vaccines in dogs. The administration of ?-glucan, 1 month before or simultaneously to Rabisin® vaccination give promising results for the generation of new TIbA candidates and their potential to provide increased immunogenicity of specific vaccines.

SUBMITTER: Paris S

PROVIDER: S-EPMC7580252 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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β-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs.

Paris Simon S Chapat Ludivine L Martin-Cagnon Nathalie N Durand Pierre-Yves PY Piney Lauriane L Cariou Carine C Bergamo Pierre P Bonnet Jeanne-Marie JM Poulet Hervé H Freyburger Ludovic L De Luca Karelle K

Frontiers in immunology 20201008

The mechanisms of trained immunity have been extensively described <i>in vitro</i> and the beneficial effects are starting to be deciphered in <i>in vivo</i> settings. Prototypical compounds inducing trained immunity, such as β-glucans, act through epigenetic reprogramming and metabolic changes of innate immune cells. The recent advances in this field have opened new areas for the development of Trained immunity-based adjuvants (TIbAs). In this study, we assessed in dogs the potential immune tra ...[more]

PMID: 33162977

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Project description:Background: Innate immune memory, also termed "trained immunity", is thought to protect against experimental models of infection, including sepsis. Trained immunity via reprogramming monocytes/macrophages has been reported to result in enhanced inflammatory status and antimicrobial activity against infection in sepsis. However, a safe and efficient way to induce trained immunity remains unclear. Methods: β-glucan is a prototypical agonist for inducing trained immunity. Ferumoxytol, superparamagnetic iron oxide (SPIO) with low cytotoxicity, has been approved by FDA for clinical use. We synthesized novel nanoparticles BSNPs by coupling β-glucan with SPIO. BSNPs were further conjugated with fluorescein for quantitative analysis and trace detection of β-glucan on BSNPs. Inflammatory cytokine levels were measured by ELISA and qRT-PCR, and the phagocytosis of macrophages was detected by flow cytometry and confocal microscopy. The therapeutic effect of BSNPs was evaluated on the well-established sepsis mouse model induced by both clinical Escherichia coli (E. coli) and cecal ligation and puncture (CLP). Results: BSNPs were synthesized successfully with a 3:20 mass ratio of β-glucan and SPIO on BSNPs, which were mainly internalized by macrophages and accumulated in the lungs and livers of mice. BSNPs effectively reprogrammed macrophages to enhance the production of trained immunity markers and phagocytosis toward bacteria. BSNP-induced trained immunity protected mice against sepsis caused by E. coli and CLP and also against secondary infection. We found that BSNP treatment elevated Akt, S6, and 4EBP phosphorylation, while mTOR inhibitors decreased the trained immunity markers and phagocytosis enhanced by BSNPs. Furthermore, the PCR Array analysis revealed Igf1, Sesn1, Vegfa, and Rps6ka5 as possible key regulators of mTOR signaling during trained immunity. BSNP-induced trained immunity mainly regulated cellular signal transduction, protein modification, and cell cycle by modulating ATP binding and the kinase activity. Our results indicated that BSNPs induced trained immunity in an mTOR-dependent manner. Conclusion: Our data highlight that the trained immunity of macrophages is an effective strategy against sepsis and suggest that BSNPs are a powerful tool for inducing trained immunity to prevent and treat sepsis and secondary infections.

Dataset Information

?-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs.

Publications

β-Glucan as Trained Immunity-Based Adjuvants for Rabies Vaccines in Dogs.

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