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针对老年人使用带有细胞因子免疫调节剂的全灭活流感疫苗定制疫苗。

Tailored vaccines targeting the elderly using whole inactivated influenza vaccines bearing cytokine immunomodulators.

机构信息

1 Department of Biomedical Sciences and Pathobiology, Virginia Tech , Blacksburg, Virginia.

出版信息

J Interferon Cytokine Res. 2014 Feb;34(2):129-39. doi: 10.1089/jir.2012.0119. Epub 2013 Oct 8.

Abstract

Influenza and its complications disproportionately affect the elderly, leading to high morbidity and mortality in this ever-increasing population. Despite widespread vaccination efforts, the current influenza vaccines are less effective in the elderly; hence newer vaccine strategies are needed to improve their efficacy in this age group. We have previously shown that co-presentation of cytokines on the surface of inactivated influenza virus particles affords better protection from lethal homotypic viral challenge in young adult mice than conventional non-adjuvanted whole inactivated vaccine. Here, we determined the efficacy of these vaccine formulations in Balb/c mice "aged" to 17 months ("aged mice") along with the addition of a membrane-bound interleukin-12 (IL-12) vaccine formulation. Our investigations found that a single low-dose intramuscular vaccination with inactivated whole influenza vaccine co-presenting IL-12 was sufficient to provide enhanced protection from subsequent influenza challenge as compared with non-adjuvanted whole inactivated vaccine. Our results indicate that incorporation of cytokines such as IL-12 in a membrane-bound formulation in whole inactivated vaccine may provide a means to lower the vaccine dose while eliciting enhanced protective responses in the elderly, an age group that responds poorly to current vaccination regimens.

摘要

流感及其并发症在老年人中发病率和死亡率较高,在这个不断增长的人群中发病率和死亡率较高。尽管广泛接种疫苗,但目前的流感疫苗在老年人中的效果较差;因此,需要新的疫苗策略来提高该年龄段的疫苗效果。我们之前已经表明,细胞因子在灭活流感病毒颗粒表面的共呈递比传统的无佐剂全灭活疫苗能更好地保护年轻成年小鼠免受同源致命性病毒攻击。在这里,我们在 17 个月大的 Balb/c 小鼠(“老年小鼠”)中确定了这些疫苗制剂的功效,并添加了一种膜结合白细胞介素 12(IL-12)疫苗制剂。我们的研究发现,与非佐剂全灭活疫苗相比,单次低剂量肌内接种共呈递白细胞介素 12 的灭活全流感疫苗足以提供增强的保护,免受随后的流感攻击。我们的结果表明,将细胞因子(如白细胞介素 12)纳入膜结合制剂的全灭活疫苗中可能是一种降低疫苗剂量的方法,同时在老年人中引发增强的保护反应,老年人对当前的疫苗接种方案反应不佳。

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