Immunization of aged pigs with attenuated pseudorabies virus vaccine combined with CpG oligodeoxynucleotide restores defective Th1 immune responses.
Immunization of aged pigs with attenuated pseudorabies virus vaccine combined with CpG oligodeoxynucleotide restores defective Th1 immune responses.
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用减毒伪狂犬病病毒疫苗联合 CpG 寡脱氧核苷酸对老年猪进行免疫可恢复有缺陷的 Th1 免疫反应。
DOI：
10.1371/journal.pone.0065536
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Ming F;Yang J;Chu P;Ma M;Shi J;Cai H;Huang C;Li H;Jiang Z;Wang H;Wang W;Zhang S;Zhang L
对老年受试者进行免疫的尝试常常导致无法引发保护性免疫反应。小鼠模型研究表明，含有 CpG 基序 (CpG ODN) 的寡核苷酸可以像年轻小鼠一样有效地刺激老年小鼠的免疫系统。由于猪的许多生理和病理生理数据可以转移到人类身上，因此对猪的研究对于确认小鼠数据非常重要。在这里，我们研究了用 CpG ODN 配制的减毒伪狂犬病病毒疫苗（PRV 疫苗）对老年猪模型进行免疫是否可以促进免疫反应的成功发展，这些免疫反应与以类似方式在幼猪中诱导的免疫反应相当。分别用 PRV 疫苗或与 CpG ODN 组合对幼猪和老年猪进行 IM 免疫。在免疫后第3、7、14天，通过ELISA测定血清的IgG滴度，在第7天测定IgG1和IgG2亚型滴度。第 7 天在装有 K-EDTA 的真空试管中收集的所有血样均进行流式细胞仪分析。第 7 天，在装有肝素的真空试管中收集血样，分析抗原特异性细胞因子的产生和外周血单核细胞 (PBMC) 的增殖反应。当CpG ODN用作老年猪疫苗接种的佐剂时，可以增强Th1反应（PRV特异性IgG2/IgG1比值、增殖反应、Th1细胞因子产生），这与CD4+ T细胞百分比增加、CD4+CD8+CD45RO+ T细胞百分比降低和PRV特异性CD4+ T细胞激活相关。我们的结果证明了 CpG ODN 作为安全疫苗佐剂的实用性，可在老年猪模型中促进有效的全身免疫反应。这种药物可能具有重要的临床用途，可以克服因疫苗接种而出现的一些与年龄相关的免疫功能抑制。
Attempts to immunize aged subjects often result in the failure to elicit a protective immune response. Murine model studies have shown that oligonucleotides containing CpG motifs (CpG ODN) can stimulate immune system in aged mice as effectively as in young mice. Since many physiological and pathophysiological data of pigs can be transferred to humans, research in pigs is important to confirm murine data. Here we investigated whether immunization of aged pig model with attenuated pseudorabies virus vaccine (PRV vaccine) formulated with CpG ODN could promote a successful development of immune responses that were comparable to those induced in young pigs in a similar manner. Young and aged pigs were immunized IM with PRV vaccine alone, or in combination with CpG ODN respectively. At days 3, 7, 14 post immunization sera were assayed by ELISA for IgG titres, at day 7 for IgG1 and IgG2 subtypes titres. All blood samples collected in evacuated test tubes with K-EDTA at day 7 were analyzed for flow cytometer assay. Blood samples at day 7 collected in evacuated test tubes with heparin were analysed for antigen-specific cytokines production and peripheral blood mononuclear cells (PBMCs) proliferative responses. CpG ODN could enhance Th1 responses (PRV-specific IgG2/IgG1 ratio, proliferative responses, Th1 cytokines production) when used as an adjuvant for the vaccination of aged pigs, which were correlated with enhanced CD4+ T cells percentage, decreased CD4+CD8+CD45RO+ T cells percentage and improved PRV-specific CD4+ T cells activation. Our results demonstrate a utility for CpG ODN, as a safe vaccine adjuvant for promoting effective systemic immune responses in aged pig model. This agent could have important clinical uses in overcoming some of age-associated depressions in immune function that occur in response to vaccination.
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影响因子：
5.5
作者：
Morgan, Edward L.;Thoman, Marilyn L.;Phillips, Joy A.
通讯作者：
Phillips, Joy A.
DOI：
10.1084/jem.168.6.2373
发表时间：
1988-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coutelier JP;van der Logt JT;Heessen FW;Vink A;van Snick J
通讯作者：
van Snick J
影响因子：
1.8
作者：
Estes, DM
通讯作者：
Estes, DM
影响因子：
4.4
作者：
Deng, YP;Jing, Y;Gravenstein, S
通讯作者：
Gravenstein, S
影响因子：
4.4
作者：
Holtmeier, W;Käller, J;Rothkötter, HJ
通讯作者：
Rothkötter, HJ