High‐ and low‐molecular‐weight chitosan act as adjuvants during single‐dose influenza A virus protein vaccination through distinct mechanisms,Biotechnology and Bioengineering

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High‐ and low‐molecular‐weight chitosan act as adjuvants during single‐dose influenza A virus protein vaccination through distinct mechanisms
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2020-12-07 , DOI: 10.1002/bit.27647
Anna T Lampe _{1,

2} , Eric J Farris ₃ , Deborah M Brown _{1,

2,

4} , Angela K Pannier ₃

Affiliation

The investigation of new adjuvants is essential for the development of efficacious vaccines. Chitosan (CS), a derivative of chitin, has been shown to act as an adjuvant, improving vaccine‐induced immune responses. However, the effect of CS molecular weight (MW) on this adjuvanticity has not been investigated, despite MW having been shown to impact CS biological properties. Here, two MW variants of CS were investigated for their ability to enhance vaccine‐elicited immune responses in vitro and in vivo, using a single‐dose influenza A virus (IAV) protein vaccine model. Both low‐molecular‐weight (LMW) and high‐molecular‐weight (HMW) CS‐induced interferon regulatory factor pathway signaling, antigen‐presenting cell activation, and cytokine messenger RNA (mRNA) production, with LMW inducing higher mRNA levels at 24 h and HMW elevating mRNA responses at 48 h. LMW and HMW CS also induced adaptive immune responses after vaccination, indicated by enhanced immunoglobulin G production in mice receiving LMW CS and increased CD4 interleukin 4 (IL‐4) and IL‐2 production in mice receiving HMW CS. Importantly, both LMW and HMW CS adjuvantation reduced morbidity following homologous IAV challenge. Taken together, these results support that LMW and HMW CS can act as adjuvants, although this protection may be mediated through distinct mechanisms based on CS MW.

中文翻译：

高分子量和低分子量壳聚糖通过不同的机制在单剂量甲型流感病毒蛋白疫苗接种中充当佐剂

新佐剂的研究对于有效疫苗的开发至关重要。壳聚糖 (CS) 是几丁质的衍生物，已被证明可作为佐剂，改善疫苗诱导的免疫反应。然而，尽管 MW 已被证明会影响 CS 生物学特性，但尚未研究 CS 分子量 (MW) 对这种佐剂性的影响。在这里，使用单剂量甲型流感病毒 (IAV) 蛋白疫苗模型研究了 CS 的两种 MW 变体在体外和体内增强疫苗引发的免疫反应的能力。低分子量 (LMW) 和高分子量 (HMW) CS 诱导的干扰素调节因子通路信号传导、抗原呈递细胞活化和细胞因子信使 RNA (mRNA) 产生，LMW 在 24 小时诱导更高的 mRNA 水平，而 HMW 在 48 小时提高 mRNA 反应。LMW 和 HMW CS 也在接种疫苗后诱导适应性免疫反应，这表明接受 LMW CS 的小鼠免疫球蛋白 G 产生增加，接受 HMW CS 的小鼠产生 CD4 白细胞介素 4 (IL-4) 和 IL-2 增加。重要的是，LMW 和 HMW CS 佐剂化都降低了同源 IAV 攻击后的发病率。总之，这些结果支持LMW和HMW CS可以作为佐剂，尽管这种保护可以通过基于CS MW的不同机制来介导。LMW 和 HMW CS 佐剂化都降低了同源 IAV 攻击后的发病率。总之，这些结果支持LMW和HMW CS可以作为佐剂，尽管这种保护可以通过基于CS MW的不同机制来介导。LMW 和 HMW CS 佐剂化都降低了同源 IAV 攻击后的发病率。总之，这些结果支持LMW和HMW CS可以作为佐剂，尽管这种保护可以通过基于CS MW的不同机制来介导。

更新日期：2020-12-07

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