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Porcine Dendritic Cells as an In Vitro Model to Assess the Immunological Behaviour of Streptococcus suis Subunit Vaccine Formulations and the Polarizing Effect of Adjuvants

机译:猪树突状细胞作为评估猪链球菌亚单位疫苗制剂的免疫行为和佐剂极化作用的体外模型

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摘要

An in vitro porcine bone marrow-derived dendritic cell (DC) culture was developed as a model for evaluating immune polarization induced by adjuvants when administered with immunogens that may become vaccine candidates if appropriately formulated. The swine pathogen Streptococcus suis was chosen as a prototype to evaluate proposed S. suis vaccine candidates in combination with the adjuvants Poly I:C, Quil A ®, Alhydrogel ®, TiterMax Gold ® and Stimune ®. The toll-like receptor ligand Poly I:C and the saponin Quil A ® polarized swine DC cytokines towards a type 1 phenotype, with preferential production of IL-12 and TNF-α. The water-in-oil adjuvants TiterMax Gold ® and Stimune ® favoured a type 2 profile as suggested by a marked IL-6 release. In contrast, Alhydrogel ® induced a type 1/type 2 mixed cytokine profile. The antigen type differently modified the magnitude of the adjuvant effect, but overall polarization was preserved. This is the first comparative report on swine DC immune activation by different adjuvants. Although further swine immunization studies would be required to better characterize the induced responses, the herein proposed in vitro model is a promising approach that helps assessing behaviour of the vaccine formulation rapidly at the pre-screening stage and will certainly reduce numbers of animals used while advancing vaccinology science.
机译:建立了体外猪骨髓源性树突状细胞(DC)培养物,作为评估佐剂诱导的免疫极化的模型,当将其与适当配制的疫苗可能成为候选疫苗的免疫原一起施用时。选择猪病原体猪链球菌为原型,与佐剂Poly I:C,QuilA®,Alhydrogel®,TiterMaxGold®和Stimune®一起评估拟议的猪链球菌疫苗候选物。收费型受体配体Poly I:C和皂苷Quil A®使猪DC细胞因子偏向1型表型,并优先产生IL-12和TNF-α。油性水佐剂TiterMax Gold®和Stimune®具有明显的IL-6释放,表明具有2型特性。相反,Alhydrogel®诱导了1型/ 2型混合细胞因子谱。抗原类型不同地改变了佐剂作用的大小,但是总体极化得以保留。这是有关不同佐剂对猪DC免疫激活的第一个比较报告。尽管需要进行进一步的猪免疫研究以更好地表征诱导的反应,但本文提出的体外模型是一种有前途的方法,可帮助在预筛选阶段快速评估疫苗制剂的行为,并肯定会减少前进时使用的动物数量疫苗科学。

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