Zhang Xue-Qing, Dahle Christopher E, Weiner George J, Salem Aliasger K
Division of Pharmaceutics, College of Pharmacy, University of Iowa, 115 S. Grand Avenue, Iowa City, IA 52242, USA.
J Pharm Sci. 2007 Dec;96(12):3283-92. doi: 10.1002/jps.20978.
CpG ODN are toll-like receptor 9 (TLR9) agonists that can enhance antigen presentation by antigen presenting cells (APCs) such as dendritic cells (DCs). The most potent antigen-specific responses are seen when CpG ODN and the antigen are co-localized in the same APC. CpG ODN-antigen fusion molecules and biodegradable microparticles entrapping CpG ODN and antigen can ensure both components are delivered to the same APC. In this study, we compared the efficacy of the CpG-ODN fusion molecules against biodegradable microparticles entrapping antigen and CpG ODN. Microparticles were prepared using a double emulsion solvent evaporation methodology. CpG ODN-OVA fusion molecules were prepared by mixing maleimide-activated protein with thiolated CpG ODN. Both CpG ODN-OVA fusion molecules and microparticles co-entrapping CpG ODN and OVA generated stronger IgG2a and interferon-gamma (IFN-gamma) responses than delivery of soluble CpG ODN and OVA. The microparticles generated stronger IgG2a and IFN-gamma immune responses than did CpG ODN-antigen fusion molecules.
CpG寡脱氧核苷酸是Toll样受体9（TLR9）激动剂，可增强抗原呈递细胞（APC）如树突状细胞（DC）的抗原呈递。当CpG寡脱氧核苷酸和抗原共定位于同一APC时，可观察到最有效的抗原特异性反应。CpG寡脱氧核苷酸-抗原融合分子以及包裹CpG寡脱氧核苷酸和抗原的可生物降解微粒可确保两种成分都被递送至同一APC。在本研究中，我们比较了CpG寡脱氧核苷酸融合分子与包裹抗原和CpG寡脱氧核苷酸的可生物降解微粒的功效。微粒采用复乳溶剂蒸发法制备。通过将马来酰亚胺活化蛋白与硫醇化的CpG寡脱氧核苷酸混合来制备CpG寡脱氧核苷酸-卵清蛋白（OVA）融合分子。与递送可溶性CpG寡脱氧核苷酸和OVA相比，CpG寡脱氧核苷酸-OVA融合分子以及共包裹CpG寡脱氧核苷酸和OVA的微粒均产生更强的IgG2a和干扰素-γ（IFN-γ）反应。微粒产生的IgG2a和IFN-γ免疫反应比CpG寡脱氧核苷酸-抗原融合分子更强。
