CpG oligonucleotide, host defense peptide and polyphosphazene act synergistically, inducing long-lasting, balanced immune responses in cattle
CpG oligonucleotide, host defense peptide and polyphosphazene act synergistically, inducing long-lasting, balanced immune responses in cattle
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DOI：
10.1016/j.vaccine.2009.01.117
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发表时间：
2009-03-23
期刊：
影响因子：
5.5
通讯作者：
Littel-van den Hurk, S. van Drunen
中科院分区：
文献类型：
--
作者：
Kovacs-Nolan, J.;Mapletoft, J. W.;Littel-van den Hurk, S. van Drunen
由亚单位或蛋白质抗原组成的疫苗比传统疫苗免疫原性低，因此需要与佐剂一起配制。然而，常规佐剂通常引起不期望的注射部位反应和Th 2偏向的免疫应答。因此，需要能够安全地增强和选择性地偏向所产生的免疫应答的新型疫苗佐剂。在此，评估了CpG ODN、indolicidin和聚磷腈（CpG +吲哚+ PP）的佐剂组合在与抗原鸡蛋溶菌酶（HEL）配制时增强和调节免疫应答的能力。用与CpG +吲哚+ PP共佐剂的HEL免疫的牛产生了更高的抗原特异性体液反应和持久的细胞介导的免疫反应，重新刺激的PBMC分泌的IFN-γ水平升高证明了这一点，甚至优于EMULSIGEN（R），一种用作阳性对照的水包油佐剂。上级。疫苗的物理表征表明，具有CpG +吲哚+ PP的HEL制剂导致抗原-佐剂复合物的形成，这可能有助于其增强的免疫原性。此外，将聚磷腈添加到CpG ODN和indolicidin中，在体外剂量依赖性地增强细胞因子IFN-α、TNF-α和IFN-γ的分泌，表明聚磷腈还可以与CpG ODN和indolicidin协同刺激先天免疫应答。(C)2009爱思唯尔有限公司保留所有权利。
Vaccines consisting of subunit or protein antigens are less immunogenic than traditional vaccines, and therefore require formulation with an adjuvant. Conventional adjuvants, however, often cause undesirable injection site reactions and Th2-biased immune responses. Therefore, novel vaccine adjuvants which can safely enhance and selectively bias the resulting immune response are required. Here the adjuvant combination of CpG ODN, indolicidin and polyphosphazene (CpG + indol + PP) was evaluated for its ability to enhance and modulate the immune response when formulated with the antigen hen egg lysozyme (HEL). Cattle immunized with HEL co-adjuvanted with CpG + indol + PP developed higher antigen-specific humoral responses, and long-lasting cell-mediated immune responses, as evidenced by elevated levels of IFN-gamma secretion by re-stimulated PBMCs, that were superior even to EMULSIGEN (R), an oil-in-water based adjuvant that Was used as positive control. Physical characterization of the vaccines indicated that formulation of HEL with CpG + indol + PP resulted in the formation of antigen-adjuvant complexes, which may have contributed to their enhanced immunogenicity. Furthermore, the addition of polyphosphazene to CpG ODN and indolicidin dose-dependently enhanced the secretion of the cytokines IFN-alpha, TNF-alpha and IFN-gamma in vitro, indicating that polyphosphazene can also synergize with CpG ODN and indolicidin to stimulate innate immune responses. (C) 2009 Elsevier Ltd. All rights reserved.