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粒细胞-巨噬细胞集落刺激因子,一种向Th-17模式极化的强效佐剂:在HIV-1疫苗模型中的经验。

Granulocyte-macrophage colony-stimulating factor, a potent adjuvant for polarization to Th-17 pattern: an experience on HIV-1 vaccine model.

作者信息

Mahdavi Mehdi, Tajik Amir Hossein, Ebtekar Massoumeh, Rahimi Roghieh, Adibzadeh Mohammad Mehdi, Moozarmpour Hamid Reza, Beikverdi Mohammad Sadegh, Olfat Soophie, Hassan Zuhair Mohammad, Choopani Mohammad, Kameli Morteza, Hartoonian Christine

机构信息

Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.

Department of Clinical Biochemistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

APMIS. 2017 Jun;125(6):596-603. doi: 10.1111/apm.12660. Epub 2017 May 11.

DOI:10.1111/apm.12660
PMID:28493367
Abstract

Cytokines are mediators for polarization of immune response in vaccines. Studies show that co-immunization of DNA vaccines with granulocyte-macrophage colony-stimulating factor (GM-CSF) can increase immune responses. Here, experimental mice were immunized with HIV-1 DNA vaccine with GM-CSF and boosted with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL-4, IFN-γ, IL-17 cytokines, total antibody, and IgG1 and IgG2a isotypes were assessed with ELISA. Results show that GM-CSF as adjuvant in DNA immunization significantly increased lymphocyte proliferation and IFN-γ cytokines, but CTL response was tiny increased. Also GM-CSF as adjuvant decreased IL-4 cytokine vs mere vaccine group. IL-17 in the group that immunized with mixture of DNA vaccine/GM-CSF was significantly increased vs DNA vaccine group. Result of total antibody shows that GM-CSF increased antibody response in which both IgG1 and IgG2a increased. Overall, results confirmed the beneficial effect of GM-CSF as adjuvant to increase vaccine immunogenicity. The hallmark result of this study was to increase IL-17 cytokine with DNA vaccine/GM-CSF immunized group. This study for the first time provides the evidence of the potency of GM-CSF in the induction of IL-17 in response to a vaccine, which is important for control of infection such as HIV-1.

摘要

细胞因子是疫苗中免疫反应极化的介质。研究表明,DNA疫苗与粒细胞-巨噬细胞集落刺激因子(GM-CSF)联合免疫可增强免疫反应。在此,用含GM-CSF的HIV-1 DNA疫苗免疫实验小鼠,并用重组疫苗加强免疫。用ELISA评估用溴脱氧尿苷(Brdu)检测的淋巴细胞增殖、CTL活性、IL-4、IFN-γ、IL-17细胞因子、总抗体以及IgG1和IgG2a亚型。结果显示,GM-CSF作为DNA免疫中的佐剂可显著增加淋巴细胞增殖和IFN-γ细胞因子,但CTL反应仅略有增加。此外,与单纯疫苗组相比,GM-CSF作为佐剂可降低IL-4细胞因子。与DNA疫苗组相比,用DNA疫苗/GM-CSF混合物免疫的组中IL-17显著增加。总抗体结果显示,GM-CSF增强了抗体反应,其中IgG1和IgG2a均增加。总体而言,结果证实了GM-CSF作为佐剂增强疫苗免疫原性的有益作用。本研究的标志性结果是DNA疫苗/GM-CSF免疫组中IL-17细胞因子增加。本研究首次提供了GM-CSF在疫苗诱导IL-17方面效力的证据,这对于控制如HIV-1等感染很重要。

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