Adsorption onto aluminum hydroxide adjuvant protects antigens from degradation
Adsorption onto aluminum hydroxide adjuvant protects antigens from degradation
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DOI：
10.1016/j.vaccine.2020.02.001
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发表时间：
2020-04-23
期刊：
影响因子：
5.5
通讯作者：
O'Hagan, Derek T.
中科院分区：
文献类型：
--
作者：
Colaprico, Annalisa;Senesi, Silvia;O'Hagan, Derek T.
铝佐剂被广泛用于商业疫苗，因为它们与各种抗原一起被认为是安全和有效的。氢氧化铝吸附抗原的影响是一个复杂的领域，因为同时涉及几个机制，其影响既取决于抗原，也取决于配方条件。此外，氢氧化铝的作用方式本身是复杂的，有许多机制同时运行。在文献中，关于吸附对抗原完整性和稳定性的影响，有不同的理论，有通过吸附到氢氧化铝上稳定抗原的报道，但也有相反的报道，抗原被破坏。为了了解吸附对三种重组蛋白的影响，这些重组蛋白在体内免疫后能够诱导出针对B型脑膜炎奈瑟菌的功能性杀菌抗体，我们使用了一系列物理化学工具，如DSC和UPLC，以及识别蛋白质结构元件的抗体的体外结合，并在小鼠研究中支持了体外数据和体内评估。我们发现，在加热的加速降解条件下，重组蛋白虽然很健壮，但可以通过吸附在氢氧化铝上稳定下来，并保持其结构完整性，不像未吸附的蛋白。熔融温度的测量是比较蛋白质在氢氧化铝上吸附和未吸附的行为以及预测蛋白质稳定性的有用工具。(C)2020爱思唯尔有限公司。保留所有权利。
Aluminum based adjuvants are widely used in commercial vaccines, since they are known to be safe and effective with a variety of antigens. The effect of antigen adsorption onto Aluminum Hydroxide is a complex area, since several mechanisms are involved simultaneously, whose impact is both antigen and formulation conditions dependent. Moreover, the mode of action of Aluminum Hydroxide is itself complex, with many mechanisms operating simultaneously. Within the literature there are contrasting theories regarding the effect of adsorption on antigen integrity and stability, with reports of antigen being stabilized by adsorption onto Aluminum Hydroxide, but also with contrary reports of antigen being destabilized. With the aim to understand the impact of adsorption on three recombinant proteins which, following in vivo immunization, are able to induce functional bactericidal antibodies against Neisseria meningitidis type B, we used a range of physico-chemical tools, such as DSC and UPLC, along with in vitro binding of antibodies that recognize structural elements of the proteins, and supported the in vitro data with in vivo evaluation in mice studies. We showed that, following exposure to accelerated degradation conditions involving heat, the recombinant proteins, although robust, were stabilized by adsorption onto Aluminum Hydroxide and retain their structural integrity unlike the not adsorbed proteins. The measure of the Melting Temperature was a useful tool to compare the behavior of proteins adsorbed and not adsorbed on Aluminum Hydroxide and to predict protein stability. (C) 2020 Elsevier Ltd. All rights reserved.