Molecular Characterization of In Vivo Adjuvant Activity in Ferrets Vaccinated against Influenza Virus
Molecular Characterization of In Vivo Adjuvant Activity in Ferrets Vaccinated against Influenza Virus
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DOI：
10.1128/jvi.02305-09
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发表时间：
2010-09-01
影响因子：
5.4
通讯作者：
Kelvin, David J.
中科院分区：
文献类型：
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作者：
Fang, Yuan;Rowe, Thomas;Kelvin, David J.
2009年H1N1流感大流行促使人们迫切需要开发有效的单剂佐剂疫苗。在这里，我们研究了CpG寡核苷酸(ODN)与人季节性流感病毒疫苗在雪貂身上的佐剂潜力。我们发现，与单独接种疫苗相比，CpG ODN佐剂疫苗有效地增加了抗体产生和激活的I型干扰素(IFN)反应。基于这些发现，与CpG ODN和完全弗氏佐剂(CFA)相比，聚乙二醇化干扰素-α2b(PEG化干扰素-α2b)也被评价为佐剂。我们的结果表明，所有三种添加佐剂的疫苗都比单独使用疫苗更有效地阻止了季节性人类A/布里斯班/59/2007(H1N1)病毒的复制。基因表达谱显示，CpG ODN不仅上调了干扰素刺激基因(ISGs)，还增强了B细胞的活化，增加了Toll样受体4(TLR4)和干扰素调节因子4(IRF4)的表达，而聚乙二醇干扰素通过诱导主要组织相容性复合体(MHC)转录和RAS信号转导而增强了获得性免疫。相反，使用CFA作为佐剂诱导了有限的ISG表达，但增加了MHC、细胞黏附分子和B细胞激活标记的转录。综上所述，我们的结果更好地表征了不同佐剂介导的流感病毒疫苗中导致佐剂活性的特定分子途径。
The 2009 H1N1 influenza pandemic has prompted a significant need for the development of efficient, single-dose, adjuvanted vaccines. Here we investigated the adjuvant potential of CpG oligodeoxynucleotide (ODN) when used with a human seasonal influenza virus vaccine in ferrets. We found that the CpG ODN-adjuvanted vaccine effectively increased antibody production and activated type I interferon (IFN) responses compared to vaccine alone. Based on these findings, pegylated IFN-alpha 2b (PEG-IFN) was also evaluated as an adjuvant in comparison to CpG ODN and complete Freund's adjuvant (CFA). Our results showed that all three vaccines with adjuvant added prevented seasonal human A/Brisbane/59/2007 (H1N1) virus replication more effectively than did vaccine alone. Gene expression profiles indicated that, as well as upregulating IFN-stimulated genes (ISGs), CpG ODN enhanced B-cell activation and increased Toll-like receptor 4 (TLR4) and IFN regulatory factor 4 (IRF4) expression, whereas PEG-IFN augmented adaptive immunity by inducing major histocompatibility complex (MHC) transcription and Ras signaling. In contrast, the use of CFA as an adjuvant induced limited ISG expression but increased the transcription of MHC, cell adhesion molecules, and B-cell activation markers. Taken together, our results better characterize the specific molecular pathways leading to adjuvant activity in different adjuvant-mediated influenza virus vaccinations.