Immune enhancing properties of the novel Matrix-M™ adjuvant leads to potentiated immune responses to an influenza vaccine in mice
Immune enhancing properties of the novel Matrix-M™ adjuvant leads to potentiated immune responses to an influenza vaccine in mice
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DOI：
10.1016/j.vaccine.2013.01.039
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发表时间：
2013-03-25
期刊：
影响因子：
5.5
通讯作者：
Stertman, Linda
中科院分区：
文献类型：
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作者：
Magnusson, Sofia E.;Reimer, Jenny M.;Stertman, Linda
基于皂苷的新型佐剂 Matrix-M (TM) 最近被用于老年人季节性流感的 I 期研究。本研究是对 Matrix-M (TM) 配制的流感疫苗在小鼠中的功效和作用方式进行的临床前评估。关于老年人的安全性和免疫原性的手稿正在准备中。我们之前已经表明，皮下注射 Matrix-M (TM)（不含共配制抗原）会导致白细胞以剂量依赖性方式募集至引流淋巴结 (dLN)。在此，我们比较了 Matrix-M (TM) 与单独的明矾、FCA 和 AS03 或与流感裂解病毒颗粒抗原配制后肌肉注射的作用模式。 48 小时后研究 dLN 和脾脏中引发的反应。与分析的其他佐剂相比，Matrix-M (TM) 在激活中枢先天免疫细胞（如中性粒细胞、树突状细胞和巨噬细胞）方面特别有效。此外，通过对用 Matrix-M (TM)、明矾或 AS03 佐剂的流感抗原免疫的小鼠的脾细胞进行体外再刺激，研究了佐剂对流感抗原记忆免疫反应的影响。用流感抗原和 Matrix-M (TM) 免疫的小鼠的脾细胞在重新刺激后产生 Th1 和 Th2 细胞因子。这种反应明显强于所研究的其他佐剂诱导的反应。有趣的是，用 Matrix-M (TM) 佐剂疫苗免疫的小鼠的抗原刺激的脾细胞产生了中性粒细胞趋化剂 KC 水平的增加，这与注射 Matrix-M (TM) 后进入 dLN 和脾脏的中性粒细胞增加一致。此外，与单独抗原相比，用 Matrix-M (TM) 佐剂的流感抗原诱导显着更高的抗原特异性 IgG1 和 IgG2a 反应。总之，佐剂 Matrix-M (TM) 在没有抗原存在的情况下激活先天免疫系统。这种激活可以解释 Matrix-M (TM) 佐剂对流感免疫力的增强。尽管 Matrix-M (TM) 介导这种有效的免疫激活，但 GLP 毒性研究和临床数据表明 Matrix-M (TM) 佐剂具有轻度至中度的安全性。 (C) 2013 Elsevier Ltd. 保留所有权利。
The novel saponin based adjuvant Matrix-M (TM) was recently used in a Phase I study of seasonal influenza in elderly. The present study is a pre-clinical evaluation of the efficacy and mode-of-action of Matrix-M (TM) formulated influenza vaccine in mice. A manuscript on safety profile and immunogenicity in elderly humans is under preparation.We have previously shown that subcutaneous injections of Matrix-M (TM), without coformulated antigen, results in a dose-dependent recruitment of leukocytes to draining lymph nodes (dLNs). Herein we compared the mode of action of Matrix-M (TM) with Alum, FCA and AS03 alone or formulated with influenza split virion antigen injected intramuscularly. The elicited responses in dLNs and spleen were investigated 48 h later. Matrix-M (TM) was particularly efficient in activation of central innate immune cells such as neutrophils, DCs and macrophages compared to the other adjuvants analyzed. Moreover, the adjuvant influence on the recall immune response to influenza antigen was studied by in vitro re-stimulation of splenocytes from mice immunized with influenza antigen adjuvanted with Matrix-M (TM), Alum or AS03. Splenocytes from mice immunized with influenza antigen and Matrix-M (TM) produced both Th1 and Th2 cytokines upon re-stimulation. This response was significantly stronger than that induced by the other adjuvants studied. Interestingly, increased levels of the neutrophil chemoattractant KC were produced by antigen stimulated splenocytes from mice immunized with Matrix-M (TM) adjuvanted vaccine, which is in agreement with the increase of neutrophils into dLNs and spleen after Matrix-M (TM) injection. Furthermore, influenza antigen adjuvanted with Matrix-M (TM) induced significantly higher antigen-specific IgG1 and IgG2a responses compared to antigen alone. In conclusion, adjuvant Matrix-M (TM) activates the innate immune system without antigen present. This activation may explain the enhanced immunity to influenza seen with Matrix-M (TM) adjuvant. Despite this potent immune activation mediated by Matrix-M (TM), GLP-toxicity studies and clinical data suggest that Matrix-M (TM) adjuvant has a mild to moderate safety profile. (C) 2013 Elsevier Ltd. All rights reserved.