Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres
Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres
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DOI：
10.1016/s0168-3659(02)00275-4
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发表时间：
2002-12-13
影响因子：
10.8
通讯作者：
Samuel, J
中科院分区：
文献类型：
--
作者：
Diwan, M;Tafaghodi, M;Samuel, J
由CpG基序未甲基化的细菌DNA序列组成的人工合成寡核苷酸(ODN)是一种有效的免疫佐剂。免疫刺激CpG序列具有物种特异性。已经报道了针对人类、啮齿动物、家畜和伴生动物的最佳CpG序列。几乎所有这些报告都描述了可溶性形式的CpG ODN和抗原的使用。我们以破伤风类毒素(TT)为模型抗原，以ODN#1826为模型CpG序列，研究了CpG ODN和抗原在可生物降解纳米球中的共传递作为免疫的替代方法。将TT和CpGODN共包裹在聚(D，L-乳酸-乙醇酸)纳米球中。分别用TT和CpG ODN纳米球皮下免疫C57BL/6小鼠2次(试验组)，单独接种TT纳米球，单独接种TT纳米球与CpG ODN溶液混合，同时接种TT和CpG ODN溶液(参照组)，单独接种TT溶液，明胶吸附TT。从试验组分离的T细胞在体外表现出较强的抗原特异性T细胞增殖(刺激指数=45)。经统计学处理，差异有统计学意义(P
Synthetic oligodeoxynucleotides (ODN) consisting of unmethylated bacterial DNA sequences with CpG motifs are potent immunological adjuvants. Immunostimulatory CpG sequences are species-specific. Optimal CpG sequences specific for humans, rodents, livestock, and companion animals have been reported. Nearly all of these reports describe the use of soluble forms of CpG ODN and antigens. We investigated the co-delivery of CpG ODN and antigens in biodegradable nanospheres as an alternative approach for immunization using tetanus toxoid (TT) as the model antigen and ODN #1826 as the model CpG sequence. TT and CpG ODN were co-encapsulated in poly(D,L-lactic-co-glycolic acid) nanospheres. Separate groups of C57BL/6 mice were subcutaneously immunized twice with TT and CpG ODN in nanospheres (test group), TT alone in nanospheres, TT alone in nanospheres mixed with CpG ODN in solution, TT and CpG ODN both in solution (reference group), TT alone in solution, and alum adsorbed TT. T cells isolated from the test group showed strong antigen-specific T cell proliferation ex vivo (stimulation index=45). This was significantly (P