Tunable degradation of acetalated dextran microparticles enables controlled vaccine adjuvant and antigen delivery to modulate adaptive immune responses.
Tunable degradation of acetalated dextran microparticles enables controlled vaccine adjuvant and antigen delivery to modulate adaptive immune responses.
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DOI：
10.1016/j.jconrel.2018.01.027
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发表时间：
2018-03-10
期刊：
影响因子：
--
通讯作者：
Ainslie KM
中科院分区：
文献类型：
--
作者：
Chen N;Johnson MM;Collier MA;Gallovic MD;Bachelder EM;Ainslie KM
亚单位疫苗通常是免疫原性差的，并且佐剂和/或递送媒介物，如聚合物微粒（MP），可用于增强免疫应答。MP也可用于了解细胞活化动力学以及抗原和佐剂释放对适应性免疫应答的显著影响。通过控制抗原和佐剂的释放，我们可以确定对这些元素的释放进行精确的时间控制是否重要，以优化保护性免疫的峰值和持续时间并改善疫苗的安全性。为了研究可调佐剂或抗原递送对产生适应性免疫的影响，我们使用缩醛化葡聚糖（Ace-DEX）MP。使用Ace-DEX MP是因为可以基于聚合物环缩醛覆盖率（CAC）控制其可调降解。使用不同降解谱的Ace-DEX MP分别递送作为模型佐剂或抗原的Murabutide或卵清蛋白（OVA）。当Murabutide被封装在Ace-DEX MP中以测试受控的佐剂递送时，快速降解的MP在较早的时间点在体内表现出更高的体液和细胞应答，而缓慢降解的MP在较晚的时间点产生更强的应答。当将OVA包封在Ace-DEX MP中以测试受控抗原递送时，快速降解的MP在整个实验长度中诱导更大的抗体和细胞因子产生。这种不同的反应表明需要对佐剂或抗原递送及其对免疫应答调节的影响进行不同的灵活控制。
Subunit vaccines are often poorly immunogenic, and adjuvants and/or delivery vehicles, such as polymeric microparticles (MPs), can be used to enhance immune responses. MPs can also be used to understand cell activation kinetics and the significant impact antigen and adjuvant release has on adaptive immune responses. By controlling antigen and adjuvant release, we can determine if it is important to have precise temporal control over release of these elements to optimize the peak and duration of protective immunity and improve vaccine safety profiles. In order to study the effect of tunable adjuvant or antigen delivery on generation of adaptive immunity, we used acetalated dextran (Ace-DEX) MPs. Ace-DEX MPs were used because their tunable degradation can be controlled based on polymer cyclic acetal coverage (CAC). Ace-DEX MPs of varying degradation profiles were used to deliver murabutide or ovalbumin (OVA) as a model adjuvant or antigen, respectively. When murabutide was encapsulated within Ace-DEX MPs to test for controlled adjuvant delivery, fast-degrading MPs exhibited higher humoral and cellular responses in vivo at earlier time points, while slow-degrading MPs resulted in stronger responses at later time points. When OVA was encapsulated within Ace-DEX MPs to test for controlled antigen delivery, fast-degrading MPs induced greater antibody and cytokine production throughout the length of the experiment. This differential response suggests the need for distinct, flexible control over adjuvant or antigen delivery and its impact on immune response modulation.
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影响因子：
17.3
作者：
Cleland, JL
通讯作者：
Cleland, JL
DOI：
10.1097/00126334-200207010-00005
发表时间：
2002-07-01
期刊：
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
影响因子：
--
作者：
Amiel, C;De La Tribonnière, X;Bahr, GM
通讯作者：
Bahr, GM
DOI：
10.1073/pnas.0901592106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Broaders, Kyle E.;Cohen, Joel A.;Frechet, Jean M. J.
通讯作者：
Frechet, Jean M. J.
影响因子：
10
作者：
DeMuth, Peter C.;Min, Younjin;Irvine, Darrell J.;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
5.2
作者：
Bahr, GM;De La Tribonnière, X;Mouton, Y
通讯作者：
Mouton, Y