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干酪乳杆菌 DK128 对增强 T 辅助细胞 1 型免疫应答和流感疫苗效果的辅助作用在正常和 CD4 缺陷小鼠中的研究

Adjuvant effects of killed Lactobacillus casei DK128 on enhancing T helper type 1 immune responses and the efficacy of influenza vaccination in normal and CD4-deficient mice.

机构信息

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; College of Veterinary Medicine, Jeju National University, Jeju, Jeju-do, Republic of Korea.

出版信息

Vaccine. 2020 Aug 10;38(36):5783-5792. doi: 10.1016/j.vaccine.2020.06.075. Epub 2020 Jul 13.

Abstract

Lactic acid bacteria Lactobacillus casei DK128 isolated from fermented vegetable foods was suggested to stimulate innate immune responses. Here, we investigated whether heat-killed DK128 would exhibit adjuvant effects on enhancing the efficacy of influenza vaccination. Immunization of mice with split influenza virus vaccine in the presence of heat-killed DK128 induced significantly higher levels of both IgG1 and IgG2c isotype antibodies than those by vaccine only. A single dose DK128-adjuvanted influenza vaccination conferred higher efficacy of protection, as evidenced by intact lung function, less weight loss, enhanced clearance of lung viral loads, and lower levels of inflammatory cytokines and infiltrates. Immunization of CD4 T cell-knockout (CD4KO) mice with influenza vaccine and DK128, but not with vaccine alone, induced isotype-switched IgG antibodies and protection against lethal challenge in CD4KO mice. The results in this study suggest heat-killed DK128 as a potential vaccine adjuvant, promoting the induction of IgG isotype switching in CD4-deficient condition and enhancing protective efficacy of split influenza vaccination in immunocompromised and immune-competent subjects.

摘要

从发酵蔬菜食品中分离出的乳杆菌属酪蛋白亚种 DK128 被认为可以刺激先天免疫反应。在这里,我们研究了热灭活的 DK128 是否具有增强流感疫苗效力的佐剂作用。与仅用疫苗免疫相比,用裂解流感病毒疫苗加热处理的 DK128 免疫小鼠可诱导更高水平的 IgG1 和 IgG2c 同种型抗体。单次剂量的 DK128 佐剂流感疫苗接种可提供更高的保护效力,这表现在肺功能完整、体重减轻较少、肺部病毒载量清除增强以及炎症细胞因子和浸润物水平降低。用流感疫苗和 DK128 免疫 CD4 T 细胞敲除(CD4KO)小鼠,而不是仅用疫苗免疫,可诱导产生同种型转换的 IgG 抗体,并可在 CD4KO 小鼠中预防致死性攻击。本研究结果表明,热灭活的 DK128 可作为一种有潜力的疫苗佐剂,促进 CD4 缺陷情况下 IgG 同种型转换的诱导,并增强免疫功能低下和免疫功能正常的受试者中裂解流感疫苗的保护效力。

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