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Internalization and antigen presentation by mouse dendritic cells of rotavirus VP6 preparations differing in nanostructure.
Molecular Immunology ( IF 3.2 ) Pub Date : 2020-05-07 , DOI: 10.1016/j.molimm.2020.04.001
Kirsi Tamminen 1 , Suvi Heinimäki 1 , Stina Gröhn 1 , Vesna Blazevic 1
Affiliation  

Nanoparticles are highly immunogenic due to the multivalent, repetitive antigen expression and direct activation of antigen presenting cells (APCs), key players of adaptive immune responses. Different virus-like particles (VLPs) have been used as display platforms to amplify immune responses to biologically relevant, but poorly immunogenic foreign antigens. A candidate platform based on rotavirus (RV) inner-capsid protein VP6 oligomers, such as nanotubes (T-VP6) and nanospheres (S-VP6), is also considered. Different VP6 nanostructures were compared for internalization and antigen presentation by the APCs. We found, that a lack of a high-order structures, T-VP6 and S-VP6, did not negatively affect VP6 uptake and presentation by murine bone-marrow derived dendritic cells (BMDCs) in vitro. Furthermore, T-VP6 was preferable to norovirus (NoV) VLPs for BMDC internalization resulting in significantly higher VP6-specific immune responses when T-VP6 and NoV VLP pulsed BMDCs were transferred to syngeneic mice. These results support the use of different VP6 nanostructures as foreign antigen delivery platforms.

中文翻译:

轮状病毒VP6制剂的小鼠树突状细胞的内在化和抗原呈递在纳米结构上有所不同。

由于多价重复抗原表达和抗原呈递细胞(APC)的直接激活,纳米颗粒具有高度免疫原性,APC是适应性免疫反应的关键因素。不同的病毒样颗粒(VLP)已用作展示平台,以放大对生物学相关但免疫原性差的外源抗原的免疫应答。还考虑了基于轮状病毒(RV)衣壳蛋白VP6寡聚体的候选平台,例如纳米管(T-VP6)和纳米球(S-VP6)。比较了不同的VP6纳米结构的内在作用和APC的抗原呈递。我们发现,缺乏高阶结构,T-VP6和S-VP6,不会对鼠骨髓来源的树突状细胞(BMDC)的VP6摄取和呈递产生负面影响。此外,对于BMDC内在化,T-VP6比诺如病毒(NoV)VLP更可取,当将T-VP6和NoV VLP脉冲的BMDC转移到同系小鼠时,会导致明显更高的VP6特异性免疫反应。这些结果支持使用不同的VP6纳米结构作为外来抗原递送平台。
更新日期:2020-05-07
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