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氢氧化铝可增强针对脊髓灰质炎病毒的具有保护性的Th1偏向性免疫反应,从而在小鼠和大鼠中实现剂量节省。

Aluminium hydroxide potentiates a protective Th1 biased immune response against polio virus that allows for dose sparing in mice and rats.

作者信息

Andreasen Lars Vibe, Hansen Lasse Bøllehuus, Andersen Peter, Agger Else Marie, Dietrich Jes

机构信息

Department of Vaccine Development, Statens Serum Institut, Copenhagen, Denmark.

Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.

出版信息

Vaccine. 2015 Apr 8;33(15):1873-9. doi: 10.1016/j.vaccine.2015.02.011. Epub 2015 Feb 17.

DOI:10.1016/j.vaccine.2015.02.011
PMID:25698487
Abstract

BACKGROUND

The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority and will be essential for the complete eradication of polio. Since the aluminium hydroxide adjuvant is widely used in humans we tested this adjuvant with IPV in two models. Our objective was twofold; to examine the IPV dose sparing effect of aluminium hydroxide and how the adjuvant effect of aluminium hydroxide affected the immunity induced by IPV.

METHODS

Mice and rats were immunized with IPV formulated with Aluminium hydroxide and subjected to immunological analyses and serum polio virus neutralization titer determination.

RESULTS

Addition of aluminium hydroxide to IPV led to a ten times dose sparing effect compared to IPV alone, measured by virus neutralization titers in serum. Aluminium hydroxide changed the kinetics of the response against IPV leading to a faster and stronger response, which due to IPV induced immune dominance was characterized as a strong Th1-biased cellular/humoral immune response.

CONCLUSIONS

The IPV-aluminium hydroxide formulation constitutes a promising vaccine capable of generating strong Th1 immunity against infection with all three serotypes. A phase I/II clinical study was recently initiated.

摘要

背景

研发新型低成本的基于灭活脊髓灰质炎病毒的疫苗(IPV)是重中之重,对于彻底根除脊髓灰质炎至关重要。由于氢氧化铝佐剂在人类中广泛使用,我们在两种模型中用IPV对这种佐剂进行了测试。我们的目标有两个;一是研究氢氧化铝对IPV的剂量节省效应,二是研究氢氧化铝的佐剂效应如何影响由IPV诱导的免疫。

方法

用含有氢氧化铝的IPV对小鼠和大鼠进行免疫,并进行免疫学分析和血清脊髓灰质炎病毒中和滴度测定。

结果

与单独的IPV相比,向IPV中添加氢氧化铝导致剂量节省效应提高了10倍,这是通过血清中的病毒中和滴度来衡量的。氢氧化铝改变了针对IPV的反应动力学,导致反应更快更强,由于IPV诱导的免疫优势,其特征为强烈的Th1偏向性的细胞/体液免疫反应。

结论

IPV - 氢氧化铝制剂是一种有前景的疫苗,能够产生针对所有三种血清型感染的强大Th1免疫。最近启动了一项I/II期临床研究。

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