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首页> 外文期刊>Vaccine >Comparative studies of Avipox-GM-CSF versus recombinant GM-CSF protein as immune adjuvants with different vaccine platforms
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Comparative studies of Avipox-GM-CSF versus recombinant GM-CSF protein as immune adjuvants with different vaccine platforms

机译：具有不同疫苗平台的Avipox-GM-CSF与重组GM-CSF蛋白作为免疫佐剂的比较研究

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent immune stimulant when administered with different vaccines. Optimal use of GM-CSF resides in its ability to act locally to stimulate the proliferation and maturation of professional antigen-presenting cells (APCs) (i.e., Langerhans' cells) at the injection site. GM-CSF was engineered into a replication-incompetent recombinant avian (fowlpox) virus (rF-GM-CSF) and a single subcutaneous injection resulted in a sustained enrichment of activated dendritic cells within the regional draining lymph nodes. Those changes were attributed to local GM-CSF production at the injection site by rF-GM-CSF-infected cells. Studies were carried out in which mice were administered different types of beta-galactosidase (beta-gal)-based vaccines--whole protein, peptide, recombinant poxviruses--and GM-CSF was administered either as a single injection of rF-GM-CSF or four daily bolus injections of the recombinant protein. The use of rF-GM-CSF either improved the immune adjuvant effect, as observed for poxvirus-based vaccines, or was equivalent to rGM-CSF, as observed with the beta-gal protein vaccine. It is important to note that with either the replication-competent (vaccinia) or replication-incompetent (fowlpox) vaccines expressing LacZ, strong CTL responses directed against beta-gal were induced only when rF-GM-CSF was used as the immune adjuvant. Engineering GM-CSF into a recombinant fowlpox virus offers an excellent vehicle for the delivery of this cytokine as an immune adjuvant with specific vaccine platforms. In particular, delivery of GM-CSF via the rF-GM-CSF construct would be preferred over bolus injections of rGM-CSF when used as an immune adjuvant with whole protein or recombinant poxvirus-based vaccines. The study underscores the importance of defining the appropriate delivery form of an immune adjuvant, such as GM-CSF, relative to the immunization strategy to maximize the host immune responses against a specific antigen.
机译：与其他疫苗一起使用时，粒细胞巨噬细胞集落刺激因子（GM-CSF）是一种有效的免疫刺激剂。 GM-CSF的最佳用途在于其在注射部位局部起作用以刺激专业抗原呈递细胞（APC）（即Langerhans's细胞）增殖和成熟的能力。 GM-CSF被工程化为无复制能力的重组禽（fowlpox）病毒（rF-GM-CSF），单次皮下注射导致区域引流淋巴结内活化树突状细胞持续富集。这些变化归因于被rF-GM-CSF感染的细胞在注射部位产生的局部GM-CSF。进行了研究，其中给小鼠施用了不同类型的基于β-半乳糖苷酶（β-gal）的疫苗-整个蛋白质，肽，重组痘病毒-且GM-CSF是以rF-GM- CSF或每日四次推注重组蛋白。如基于痘病毒的疫苗所观察到的，rF-GM-CSF的使用可以提高免疫佐剂的作用，或者与β-gal蛋白疫苗所观察到的，它的使用等同于rGM-CSF。重要的是要注意，无论是表达LacZ的具有复制能力的疫苗（牛痘）还是没有复制能力的疫苗（禽痘），仅当将rF-GM-CSF用作免疫佐剂时，才能诱导针对β-gal的强CTL反应。将GM-CSF工程化为重组鸡痘病毒可提供出色的载体，可通过特定的疫苗平台将这种细胞因子作为免疫佐剂进行传递。特别地，当与全蛋白或基于重组痘病毒的疫苗一起用作免疫佐剂时，通过rF-GM-CSF构建体递送GM-CSF比推注rGM-CSF更可取。该研究强调了相对于最大程度地针对特定抗原的宿主免疫反应的免疫策略，定义适当的免疫佐剂（例如GM-CSF）递送形式的重要性。

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