Overexpression of Interleukin-33 in Recombinant Rabies Virus Enhances Innate and Humoral Immune Responses through Activation of Dendritic Cell-Germinal Center Reactions.

Overexpression of Interleukin-33 in Recombinant Rabies Virus Enhances Innate and Humoral Immune Responses through Activation of Dendritic Cell-Germinal Center Reactions.
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DOI:
10.3390/vaccines10010034
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发表时间:
2021-12-28
期刊:
影响因子:
7.8
通讯作者:
Li Y
Li Y
中科院分区:
医学3区
文献类型:
--
作者:
Mi Z;Zhao L;Sun M;Gao T;Wang Y;Sui B;Li Y

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狂犬病是由狂犬病病毒(RABV)引起的人畜共患传染病,病死率高达100%。全球平均每年有6万人死于狂犬病。预防和限制狂犬病的最有效方法是接种疫苗,但目前这种方法既昂贵又低效,需要3剂系列注射,每年需要接种一次。因此,研制单剂长效狂犬病疫苗迫在眉睫。本研究构建了过表达白细胞介素-33(IL-33)的重组狂犬病病毒(rRABV),命名为rLBNSE-IL-33,并在小鼠模型中评价了其作用。结果表明,rLBNSE-IL 33可以通过激活天然免疫系统的组成部分树突状细胞(DCs)来增强RABV诱导的免疫抗体的快速产生,早在免疫后3天(dpi)。此外,rLBNSE-IL 33通过调节T细胞依赖性生发中心(GC)反应诱导高水平的病毒中和抗体(VNA)产生,持续8周,从而导致更好的狂犬病保护。我们的数据表明,IL-33是一种新的佐剂,可用于通过激活DC-GC反应来增强先天性和体液免疫应答,因此,rLBNSE-IL-33可被开发为安全有效的动物疫苗。
Rabies is a zoonotic infectious disease caused by rabies virus (RABV), and its mortality rate is as high as 100%. Globally, an average of 60,000 people die from rabies each year. The most effective method to prevent and limit rabies is vaccination, but it is currently expensive and inefficient, consisting of a 3-dose series of injections and requiring to be immunized annually. Therefore, it is urgent to develop a single dose of long-acting rabies vaccine. In this study, recombinant rabies virus (rRABV) overexpressing interleukin-33 (IL-33) was constructed and designated as rLBNSE-IL33, and its effect was evaluated in a mouse model. The results showed that rLBNSE-IL33 could enhance the quick production of RABV-induced immune antibodies as early as three days post immunization (dpi) through the activation of dendritic cells (DCs), a component of the innate immune system. Furthermore, rLBNSE-IL33 induced high-level virus-neutralizing antibodies (VNA) production that persisted for 8 weeks by regulating the T cell-dependent germinal center (GC) reaction, thus resulting in better protection against rabies. Our data suggest the IL-33 is a novel adjuvant that could be used to enhance innate and humoral immune responses by activating the DC-GC reaction, and thus, rLBNSE-IL33 could be developed as a safe and effective vaccine for animals.
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发表时间: 2020-04-14
期刊: IMMUNITY
影响因子: 32.4
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外源IL-33恢复了既定癌症的树突状细胞的活化和成熟。
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发表时间: 2017-02-01
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通讯作者: Han, Wei