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β-葡聚糖作为狂犬病疫苗佐剂在犬中的训练免疫。

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

机构信息

Boehringer Ingelheim Animal Health, R&D, Lyon, France.

Université de Lyon, APCSe, Pulmonary and Cardiovascular Agression in Sepsis, VetAgro Sup-Campus Vétérinaire de Lyon, Marcy l'Etoile, France.

出版信息

Front Immunol. 2020 Oct 8;11:564497. doi: 10.3389/fimmu.2020.564497. eCollection 2020.

Abstract

The mechanisms of trained immunity have been extensively described and the beneficial effects are starting to be deciphered in 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 training effects of β-glucans as well as their capacity to enhance the adaptive immune response of an inactivated rabies vaccine (Rabisin). Injection of β-glucan from was performed 1 month before vaccination with Rabisin supplemented or not with the same β-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 β-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 β-glucan or not. Our preliminary results support that adjuvantation of Rabisin vaccine with β-glucan elicit a higher B-lymphocyte immune response, the prevailing factor of protection against rabies. β-glucan also tend to stimulate the T cell response as shown by the cytokine secretion profile of PBMCs re-stimulated Our data are providing new insights on the impact of trained immunity on the adaptive immune response to vaccines in dogs. The administration of β-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.

摘要

训练免疫的机制已经得到了广泛的描述,其有益效果也开始在各种环境中被揭示。典型的诱导训练免疫的化合物,如β-葡聚糖,通过先天免疫细胞的表观遗传重编程和代谢变化起作用。该领域的最新进展为基于训练免疫的佐剂(TIbAs)的开发开辟了新的领域。在这项研究中,我们评估了β-葡聚糖在狗体内的潜在免疫训练效果,以及它们增强灭活狂犬病疫苗(Rabisin)适应性免疫反应的能力。在接种 Rabisin 前 1 个月,给狗注射β-葡聚糖,Rabisin 中添加或不添加用作佐剂的相同β-葡聚糖。在试验的第一个月评估训练的先天免疫参数。研究的第二阶段侧重于β-葡聚糖增强适应性免疫反应的能力,通过多种免疫参数进行测量。监测 B 和 T 细胞特异性反应,以评估添加或不添加β-葡聚糖的狂犬病疫苗的免疫原性。我们的初步结果支持,β-葡聚糖佐剂 Rabisin 疫苗可引起更高的 B 淋巴细胞免疫反应,这是预防狂犬病的主要因素。β-葡聚糖还倾向于刺激 T 细胞反应,这可以通过 PBMC 再次刺激后的细胞因子分泌谱来证明。我们的数据为训练免疫对狗对疫苗的适应性免疫反应的影响提供了新的见解。β-葡聚糖的给药,无论是在 Rabisin 疫苗接种前 1 个月还是同时给药,都为生成新的 TIbA 候选物及其提供特定疫苗更高免疫原性的潜力提供了有希望的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f422/7580252/ca50a7714982/fimmu-11-564497-g001.jpg

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