In vivo programming of endogenous antibodies via oral administration of adaptor ligands.
In vivo programming of endogenous antibodies via oral administration of adaptor ligands.
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DOI：
10.1016/j.bmc.2017.09.010
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发表时间：
2017-11
影响因子：
3.5
通讯作者：
M. Nagano;Nancy Carrillo;N. Otsubo;W. Hakamata;Hitoshi Ban;Roberta P. Fuller;Nasir K. Bashiruddin;C. Barbas
中科院分区：
文献类型：
--
作者：
M. Nagano;Nancy Carrillo;N. Otsubo;W. Hakamata;Hitoshi Ban;Roberta P. Fuller;Nasir K. Bashiruddin;C. Barbas
预防接种是一种可靠的预防方法，也是一项重要的公共卫生措施。然而，大多数疫苗不能口服给药，因为它们在恶劣的肠道环境中降解或不能穿过胃肠道。在这项研究中，我们报告了第一个概念验证研究口服生产的化学程序化抗体，通过特异性共轭衔接配体内源性抗体，在体内。用2，4-二硝基苯基（DNP）、反应性半抗原1，3-二酮（DK）或新型反应性半抗原乙烯砜（VS）预免疫小鼠，然后口服由半抗原和生物素组成的接头配体，可在2 h内成功地在体内形成生物素-半抗原-抗体复合物。药代动力学评价显示，程序化抗体的表观血清浓度高达144 nM，血清半衰期高达34.4 h。这些发现为口服生物可利用药物-半抗原-抗体复合物的未来开发带来了希望，作为快速、轻松地调节侵袭性病原体和癌症的免疫靶点的策略。
Vaccination is a reliable method of prophylaxis and a crucial measure for public health. However, the majority of vaccines cannot be administered orally due to their degradation in the harsh gut environment or inability to cross the GI tract. In this study, we report the first proof-of-concept study of orally producible chemically programmed antibodies via specific conjugation of adaptor ligands to endogenous antibodies,in vivo. Pre-immuniztion with 2,4-dinitrophenyl (DNP), or the reactive hapten, 1,3-diketone (DK), or a novel reactive hapten, vinyl sulfone (VS) in mice, followed by oral administration of adaptor ligands composed of the hapten and biotin to the pre-immunized mice resulted in successfulin vivoformation of the biotin-hapten-antibody complexes within 2 h. Pharmacokinetic evaluations revealed that apparent serum concentrations of programmed antibodies were up to 144 nM and that the serum half-lives reached up to 34.4 h. These findings show promise for the future development of orally bioavailable drug-hapten-antibody complexes as a strategy to quickly and easily modulate immune targets for aggressive pathogens as well as cancer.