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首页> 外文期刊>Vaccine >Exploring the vaccine potential of Dec-205 targeting in Mycobacterium tuberculosis infection in mice.
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Exploring the vaccine potential of Dec-205 targeting in Mycobacterium tuberculosis infection in mice.

机译：探索针对Dec-205的疫苗在小鼠结核分枝杆菌感染中的疫苗潜力。

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Protein subunit vaccines are an attractive mode of immunisation against infectious diseases but the approach is hampered by the lack of suitable adjuvants for human use. We investigated if antigen targeting to the endocytic cell receptor Dec-205 on dendritic cells (DCs) could induce a protective immune response to Mycobacterium tuberculosis (MTB) infection in the absence of conventional adjuvants. Dec-205 receptor expressed by several subsets of DC has been shown in previous studies to be an efficient endocytic receptor for inducing both humoral and cellular immune responses, but this immunisation approach has not been tested in an experimental model of infection. We therefore prepared chemical conjugates of an anti-mouse Dec-205 monoclonal antibody (mAb) and the highly immunogenic antigen 85B (Ag85B) of MTB and showed that they bound efficiently to bone-marrow derived DC. Moreover, DC stimulated in vitro with Dec-205 conjugates could induce proliferation of splenocytes from Ag85B-immunised mice, while the negative control conjugates failed to do so. Following immunisation of mice with the anti-Dec-205-Ag85B conjugates administered together with a co-stimulatory anti-CD40 mAb, antigen-specific humoral and cellular responses were detected. Although the conjugates induced a strong Ag85B-specific humoral response, T cell proliferation and interferon- gamma production were observed only when the conjugates were used to boost BCG vaccine. Importantly though, the conjugate vaccine did not offer significant protection against MTB challenge when used on its own or as a boost to BCG. Therefore, we conclude that Ag85B-based vaccine targeting to Dec-205 alone is not a sufficiently robust vaccination strategy for tuberculosis, although this approach might be more successful with other antigens or infections.Digital Object Identifier http://dx.doi.org/10.1016/j.vaccine.2011.01.030
机译：蛋白亚基疫苗是一种针对传染病的诱人免疫方法，但是由于缺乏适合人类使用的佐剂，该方法受到了阻碍。我们研究了在没有常规佐剂的情况下，针对树突状细胞（DC）上的内吞细胞受体Dec-205的抗原是否可以诱导针对结核分枝杆菌（MTB）感染的保护性免疫应答。在以前的研究中，由DC的几个子集表达的Dec-205受体已被证明是诱导体液和细胞免疫反应的有效内吞受体，但是这种免疫方法尚未在感染的实验模型中进行过测试。因此，我们制备了抗小鼠Dec-205单克隆抗体（mAb）和MTB的高度免疫原性抗原85B（Ag85B）的化学偶联物，并显示它们与骨髓衍生的DC有效结合。此外，用Dec-205偶联物体外刺激DC可以诱导Ag85B免疫小鼠的脾细胞增殖，而阴性对照偶联物则不能。在将抗-Dec-205-Ag85B偶联物与共刺激性抗-CD40 mAb一起给予小鼠免疫后，检测到抗原特异性的体液和细胞反应。尽管结合物诱导了强烈的Ag85B特异性体液反应，但仅当结合物用于加强BCG疫苗时，才观察到T细胞增殖和γ干扰素产生。但是，重要的是，结合疫苗单独使用或作为BCG的增强剂时，并未提供针对MTB攻击的显着保护作用。因此，我们得出的结论是，仅针对于Dec-205的基于Ag85B的疫苗并不是针对结核病的足够稳健的疫苗接种策略，尽管这种方法在其他抗原或感染中可能更成功。 /10.1016/j.vaccine.2011.01.030

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