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作为一种抗原递送平台:感染经工程改造以表达 SARS-CoV-2 刺突蛋白的克隆后树突状细胞的成熟

as an Antigen Delivery Platform: Dendritic Cell Maturation after Infection with a Clone Engineered to Express the SARS-CoV-2 Spike Protein.

作者信息

Varotto-Boccazzi Ilaria, Garziano Micaela, Cattaneo Giulia Maria, Bisaglia Beatrice, Gabrieli Paolo, Biasin Mara, Manenti Alessandro, Rubolini Diego, Clerici Mario, Montomoli Emanuele, Zuccotti Gian Vincenzo, Trabattoni Daria, Epis Sara, Bandi Claudio

机构信息

Department of Biosciences, University of Milan, 20133 Milan, Italy.

Pediatric CRC 'Romeo ed Enrica Invernizzi', University of Milan, 20157 Milan, Italy.

出版信息

Vaccines (Basel). 2022 May 19;10(5):803. doi: 10.3390/vaccines10050803.

Abstract

BACKGROUND

Protozoa of the genus are characterized by their capacity to target macrophages and Dendritic Cells (DCs). These microorganisms could thus be exploited for the delivery of antigens to immune cells. is regarded as a non-pathogenic species; it was previously used as a biofactory for protein production and has been considered as a candidate vaccine or as an antigen delivery platform. However, results on the type of immune polarization determined by are still inconclusive.

METHODS

DCs were derived from human monocytes and exposed to live , using both the non-engineered P10 strain, and the same strain engineered for expression of the spike protein from SARS-CoV-2. We then determined: (i) parasite internalization in the DCs; and (ii) the capacity of the assayed strains to activate DCs and the type of immune polarization.

RESULTS

Protozoan parasites from both strains were effectively engulfed by DCs, which displayed a full pattern of maturation, in terms of MHC class II and costimulatory molecule expression. In addition, after parasite infection, a limited release of Th1 cytokines was observed.

CONCLUSIONS

Our results indicate that could be used as a vehicle for antigen delivery to DCs and to induce the maturation of these cells. The limited cytokine release suggests as a neutral vaccine vehicle that could be administered in association with appropriate immune-modulating molecules.

摘要

背景

属原生动物的特点是能够靶向巨噬细胞和树突状细胞(DCs)。因此,这些微生物可用于将抗原递送至免疫细胞。被视为非致病物种;它以前被用作蛋白质生产的生物工厂,并被认为是候选疫苗或抗原递送平台。然而,关于由所确定的免疫极化类型的结果仍无定论。

方法

DCs来源于人单核细胞,并使用未工程化的P10菌株以及经工程改造以表达严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白的同一菌株,使其暴露于活的中。然后我们确定:(i)DCs中寄生虫的内化;以及(ii)所检测菌株激活DCs的能力和免疫极化类型。

结果

两种菌株的原生动物寄生虫均被DCs有效吞噬,就MHC II类分子和共刺激分子表达而言,DCs呈现出完全成熟的模式。此外,在寄生虫感染后,观察到Th1细胞因子的有限释放。

结论

我们的结果表明,可用作将抗原递送至DCs并诱导这些细胞成熟的载体。有限的细胞因子释放表明是一种中性疫苗载体,可与适当的免疫调节分子联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49ea/9144667/734612863dec/vaccines-10-00803-g001.jpg

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