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低 pH 值处理全病毒流感疫苗的免疫原性。

Immunogenicity of low-pH treated whole viral influenza vaccine.

机构信息

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.

出版信息

Virology. 2011 Aug 15;417(1):196-202. doi: 10.1016/j.virol.2011.05.014. Epub 2011 Jun 30.

DOI:10.1016/j.virol.2011.05.014
PMID:21722934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3152636/
Abstract

Low pH treatment of influenza virus hemagglutinin (HA) exposes its relatively conserved stalk domain, suggesting a potential immunogen with capability to induce broader immune responses. Here, we describe characterization, immunogenicity, antigenicity, and protective immunity induced by low pH treated inactivated whole viral vaccine in comparison with the untreated vaccine. The acidic pH treated viral vaccine showed high susceptibility to proteolytic cleavage and low hemagglutination activity indicating conformational changes. Immunization of mice with low pH treated viral vaccine induced lower levels of homologous or heterologous virus-specific binding and neutralizing antibodies compared to the untreated vaccine. Also, low pH treated influenza viral antigen showed lower antigenicity compared to the untreated influenza viral antigen. Lower efficacy of cross-protection against heterosubtypic virus was observed in the low-pH treated vaccine group. The results provide evidence that there is a correlation between protective efficacy and the stability of vaccines.

摘要

低 pH 值处理流感病毒血凝素(HA)会暴露出其相对保守的茎干结构域,这表明其具有作为潜在免疫原的能力,能够诱导更广泛的免疫反应。在此,我们描述了低 pH 值处理灭活全病毒疫苗的特性、免疫原性、抗原性和诱导的保护免疫,将其与未经处理的疫苗进行了比较。酸性 pH 值处理的病毒疫苗表现出对蛋白水解切割的高敏感性和低血凝活性,表明其构象发生了变化。与未经处理的疫苗相比,用低 pH 值处理的病毒疫苗免疫的小鼠产生的同源或异源病毒特异性结合和中和抗体水平较低。此外,与未经处理的流感病毒抗原相比,低 pH 值处理的流感病毒抗原的抗原性较低。在低 pH 值处理疫苗组中,观察到针对异源病毒的交叉保护效果较低。这些结果提供了证据表明,保护效力与疫苗的稳定性之间存在相关性。

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本文引用的文献

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Heterosubtypic protective immunity against influenza A virus induced by fusion peptide of the hemagglutinin in comparison to ectodomain of M2 protein.与M2蛋白胞外域相比,血凝素融合肽诱导的甲型流感病毒异亚型保护性免疫。
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Influenza virus-like particles containing M2 induce broadly cross protective immunity.含 M2 的流感病毒样颗粒诱导广泛交叉保护免疫。
PLoS One. 2011 Jan 18;6(1):e14538. doi: 10.1371/journal.pone.0014538.
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Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus.通用抗体针对高度保守的流感融合肽进行交叉中和,可中和几种亚型的甲型流感病毒。
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Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes.接种流感病毒血凝素的合成肽可提供针对不同病毒亚型的保护。
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18979-84. doi: 10.1073/pnas.1013387107. Epub 2010 Oct 18.
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Influenza virus vaccine based on the conserved hemagglutinin stalk domain.基于保守血凝素茎域的流感病毒疫苗。
mBio. 2010 May 18;1(1):e00018-10. doi: 10.1128/mBio.00018-10.
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Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge.基于 HA2 的大肠杆菌表达流感免疫原的设计,可保护小鼠免受致病性挑战。
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Intradermal vaccination with influenza virus-like particles by using microneedles induces protection superior to that with intramuscular immunization.经皮微针接种流感病毒样颗粒诱导的保护作用优于肌肉内免疫接种。
J Virol. 2010 Aug;84(15):7760-9. doi: 10.1128/JVI.01849-09. Epub 2010 May 19.
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Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins.序贯免疫不同血凝素可诱导针对 H3 流感病毒的广谱保护性单克隆抗体。
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