Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, People's Republic of China.
J Virol. 2010 Sep;84(17):8369-88. doi: 10.1128/JVI.02305-09. Epub 2010 Jun 9.
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-alpha2b (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.
2009 年 H1N1 流感大流行促使人们迫切需要开发高效、单剂量、佐剂化的疫苗。在这里，我们研究了 CpG 寡脱氧核苷酸（ODN）与季节性流感病毒疫苗联合使用在雪貂中的佐剂潜力。我们发现，与单独使用疫苗相比，CpG ODN 佐剂疫苗可有效增加抗体产生并激活 I 型干扰素（IFN）反应。基于这些发现，我们还评估了聚乙二醇化 IFN-α2b（PEG-IFN）作为佐剂与 CpG ODN 和完全弗氏佐剂（CFA）相比的效果。我们的结果表明，与单独使用疫苗相比，所有三种添加佐剂的疫苗均能更有效地预防季节性人 A/Brisbane/59/2007（H1N1）病毒复制。基因表达谱表明，CpG ODN 不仅上调 IFN 刺激基因（ISGs），还增强 B 细胞激活并增加 Toll 样受体 4（TLR4）和干扰素调节因子 4（IRF4）表达，而 PEG-IFN 通过诱导主要组织相容性复合物（MHC）转录和 Ras 信号增强适应性免疫。相比之下，使用 CFA 作为佐剂诱导有限的 ISG 表达，但增加 MHC、细胞黏附分子和 B 细胞激活标志物的转录。总之，我们的结果更好地描述了不同佐剂介导的流感病毒疫苗接种中导致佐剂活性的特定分子途径。
