Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide
Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide
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DOI：
10.1088/0957-4484/21/19/195101
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发表时间：
2010-05-14
期刊：
影响因子：
3.5
通讯作者：
Huang, Guewha Steven
中科院分区：
文献类型：
--
作者：
Chen, Yu-Shiun;Hung, Yao-Ching;Huang, Guewha Steven
为了评估金纳米颗粒（GNP）作为大小依赖性载体的能力，将类似口蹄疫病毒（FMDV）蛋白的合成肽缀合至直径范围为2至50 nm（2、5、8、12、17、37和50 nm）的GNP。将额外的半胱氨酸添加到FMDV肽（pFMDV）的C末端以确保与GNP的最大缀合，GNP对巯基具有高亲和力。然后将所得pFMDV-GNP缀合物注射到BALB/c小鼠中。用pFMDV-钥孔血蓝蛋白（pFMDV KLH）缀合物免疫也作为对照进行。在4、6、8和10周后从小鼠获得血液，并测量针对pFMDV和载体的抗体滴度。对于pFMDV-GNP免疫，在注射2、5、8、12和17 nm pFMDV-GNP缀合物的小鼠的血清中检测到针对合成肽的特异性抗体。对于直径为8-17 nm的GNP，注意到最大抗体结合。与对pFMDV-KLH的应答相比，pFMDV-GNP诱导的抗体应答增加三倍。然而，来自任一免疫小鼠组的血清均未表现出对GNP的抗体应答，而来自pFMDV-KLH免疫小鼠的血清呈现出高水平的针对KLH的结合活性。此外，通过电感耦合等离子体质谱（ICP-MS）和透射电子显微镜（TEM）检查脾脏中pFMDV-GNP的摄取。脾中积累的GNP的量与pFMDV-GNP诱导的免疫应答的大小相关。总之，我们证明了pFMDV-GNP缀合物的大小依赖性免疫原性。此外，我们确定了直径在8至17 nm范围内的GNP对于引发针对合成pFMDV肽的集中抗体应答可能是理想的。
To assess the ability of gold nanoparticles (GNPs) to act as a size-dependent carrier, a synthetic peptide resembling foot-and-mouth disease virus (FMDV) protein was conjugated to GNPs ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). An extra cysteine was added to the C-terminus of the FMDV peptide (pFMDV) to ensure maximal conjugation to the GNPs, which have a high affinity for sulfhydryl groups. The resultant pFMDV-GNP conjugates were then injected into BALB/c mice. Immunization with pFMDV-keyhole limpet hemocyanin (pFMDV-KLH) conjugate was also performed as a control. Blood was obtained from the mice after 4, 6, 8, and 10 weeks and antibody titers against both pFMDV and the carriers were measured. For the pFMDV-GNP immunization, specific antibodies against the synthetic peptide were detected in the sera of mice injected with 2, 5, 8, 12, and 17 nm pFMDV-GNP conjugates. Maximal antibody binding was noted for GNPs of diameter 8-17 nm. The pFMDV-GNPs induced a three-fold increase in the antibody response compared to the response to pFMDV-KLH. However, sera from either immunized mouse group did not exhibit an antibody response to GNPs, while the sera from pFMDV-KLH-immunized mice presented high levels of binding activity against KLH. Additionally, the uptake of pFMDV-GNP in the spleen was examined by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscopy (TEM). The quantity of GNPs that accumulated in the spleen correlated to the magnitude of the immune response induced by pFMDV-GNP. In conclusion, we demonstrated the size-dependent immunogenic properties of pFMDV-GNP conjugates. Furthermore, we established that GNPs ranging from 8 to 17 nm in diameter may be ideal for eliciting a focused antibody response against a synthetic pFMDV peptide.