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自佐剂C18脂质乙烯砜-PP2A疫苗:针对感染的诱导免疫调节研究

Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against infection.

作者信息

Gomez-Samblas M, García-Rodríguez J J, Trelis M, Bernal D, Lopez-Jaramillo F J, Santoyo-Gonzalez F, Vilchez S, Espino A M, Bolás-Fernández F, Osuna A

机构信息

Instituto de Biotecnología, Grupo de Bioquímica y Parasitología Molecular, Departamento de Parasitología, Universidad de Granada, Campus Universitario Fuentenueva, 18071 Granada, Spain.

Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, Plaza de Ramón y Cajal s/n. Ciudad Universitaria, 28040 Madrid, Spain.

出版信息

Open Biol. 2017 Apr;7(4). doi: 10.1098/rsob.170031.

Abstract

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode (rPP2A) was used for intranasal immunization in mice previously infected with The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other experimental groups. Also, these animals presented significantly different chemokine, CCL20 and CCL11, levels. However, although the number and size of Tuft cells did not vary between groups, the intensity of fluorescence per cell was significant in the group immunized with the rPP2A-OVS. The results of the present study suggest that mice immunized with the lipopeptide are capable of activating a combined Th17/Th9 response. This strategy of immunization may be of great applicability not only in immunotherapy and immunoprophylaxis to control diseases caused by nematodes but also in pathologies necessitating action at the level of the Th9 response in the intestinal mucosa.

摘要

尽管佐剂在免疫过程中很重要,但在疫苗中能与抗原融合的佐剂却很少。一种与线虫重组丝氨酸/苏氨酸磷酸酶2A(rPP2A)催化区域相连的合成自佐剂油酸乙烯砜(OVS),此前被用于对感染过的小鼠进行鼻内免疫。用rPP2A-OVS对动物进行鼻内免疫后,线虫卵数量减少了99.01%,成虫数量减少了97.90%。肠道切片的免疫组织化学分析表明,用脂肽免疫的动物的黏液明显高于其他实验组。此外,这些动物的趋化因子CCL20和CCL11水平也有显著差异。然而,尽管不同组之间簇状细胞的数量和大小没有变化,但在用rPP2A-OVS免疫的组中,每个细胞的荧光强度很显著。本研究结果表明,用脂肽免疫的小鼠能够激活Th17/Th9联合应答。这种免疫策略不仅在免疫治疗和免疫预防以控制由线虫引起的疾病方面可能具有很大的适用性,而且在需要在肠道黏膜Th9应答水平发挥作用的病理状况中也可能适用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4808/5413912/220f93706e63/rsob-7-170031-g1.jpg

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