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对百日咳博德特氏菌灭活全细胞包封藻酸盐微球作为新型疫苗候选物的细胞介导和体液免疫反应。

Cell-Mediated and Humoral Immune Responses to Bordetella pertussis Inactivated Whole-Cells Encapsulated Alginate Microspheres as a New Vaccine Candidate.

作者信息

Dounighi Naser M, Shahcheraghi Fereshteh, Razzaghi-Abyaneh Mehdi, Nofeli Mojtaba, Zolfagharian Hossein

机构信息

Department of Microbiology, Pasteur Institute of Iran, 13164 Tehran. Iran

Department of Human Vaccine and Serum, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj. Iran.

出版信息

Curr Pharm Biotechnol. 2017;18(7):585-593. doi: 10.2174/1389201018666170815170515.

Abstract

UNLABELLED

Effectiveness of the whole-cell pertussis vaccine is apparent, but improvement in the quality of the vaccine is necessary to achieve strong immunogenicity with a low bacterial number content.

METHOD

Inactivated Bordetella pertussis (B. pertussis) cells entrapped microspheres were prepared via an emulsification method and analyzed for morphology, size, size distribution, loading efficiency, loading capacity, release kinetic, in vivo cytokines and antigen specific antibody subclasses.

RESULTS

Bordetella pertussis encapsulated microspheres exhibited a smooth surface and spherical shape, mean particle size 151.1 µm, size distribution index 0.43, loading efficiency 89.6%, loading capacity 36.3% and release kinetic similar to the Korsmeyer-Peppas model. Splenocytes of animals immunized with new microsphere-based whole-cell vaccine produced greater quantities of IFN-γ and higher amounts of IL-4 and IL-5 cytokines compared to conventional adjuvant-adsorbed vaccines. Conventional adjuvant-adsorbed vaccines produced smaller quantities of IL-4 and IL-5. Bordetella pertussis entrapped microspheres induced both cell-mediated and humoral antibody in mice, evidenced by high levels of IgG2a and IgG1. IgG2a levels in mice were enhanced using the common aluminum phosphate-adsorbed B. pertussis whole-cell vaccine, and IgG1 levels did not increase significantly. Bordetella pertussis entrapped microspheres and common B. pertussis whole-cell vaccine samples enhanced total IgG levels in mice; however, B. pertussis-entrapped microspheres produced significantly higher levels of total IgG than other test samples.

CONCLUSION

Encapsulation of inactive B. pertussis cells in microspheres appears to be a suitable approach for improving the wP vaccine quality, in particular by decreasing its toxicity to obtain good cell-mediated and humoral immunogenicity with a low bacterial number content.

摘要

未标记

全细胞百日咳疫苗的有效性是明显的,但为了在低细菌数量含量的情况下实现强免疫原性,有必要提高疫苗的质量。

方法

通过乳化法制备灭活的百日咳博德特氏菌(百日咳杆菌)细胞包封的微球,并对其形态、大小、大小分布、负载效率、负载容量、释放动力学、体内细胞因子和抗原特异性抗体亚类进行分析。

结果

百日咳杆菌包封的微球表面光滑,呈球形,平均粒径151.1 µm,大小分布指数0.43,负载效率89.6%,负载容量36.3%,释放动力学与Korsmeyer-Peppas模型相似。与传统佐剂吸附疫苗相比,用新型微球全细胞疫苗免疫的动物脾细胞产生了更多的IFN-γ以及更高量的IL-4和IL-5细胞因子。传统佐剂吸附疫苗产生的IL-4和IL-5量较少。百日咳杆菌包封的微球在小鼠中诱导了细胞介导和体液抗体,高浓度的IgG2a和IgG1证明了这一点。使用常见的磷酸铝吸附百日咳杆菌全细胞疫苗可提高小鼠体内的IgG2a水平,而IgG1水平没有显著增加。百日咳杆菌包封的微球和普通百日咳杆菌全细胞疫苗样品提高了小鼠体内的总IgG水平;然而,百日咳杆菌包封的微球产生的总IgG水平明显高于其他测试样品。

结论

将无活性的百日咳杆菌细胞包封在微球中似乎是提高全细胞百日咳疫苗质量的合适方法,特别是通过降低其毒性,以在低细菌数量含量的情况下获得良好的细胞介导和体液免疫原性。

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