NaCl strongly modifies the physicochemical properties of aluminum hydroxide vaccine adjuvants

NaCl strongly modifies the physicochemical properties of aluminum hydroxide vaccine adjuvants
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DOI:
10.1016/j.ijpharm.2016.12.019
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发表时间:
2017-01-30
影响因子:
5.8
通讯作者:
Dupont-Gillain, Christine C.
Dupont-Gillain, Christine C.
中科院分区:
医学2区
文献类型:
--
作者:
Art, Jean-Francois;vander Straeten, Aurelien;Dupont-Gillain, Christine C.

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大多数疫苗的免疫刺激能力是通过氢氧化铝(AH)佐剂上的抗原吸附而增强的。改变吸附条件,即pH值和离子强度(I),改变抗原吸附量,从而改变疫苗刺激免疫系统的能力。因此,疫苗配方是由吸附条件的经验筛选产生的。本工作旨在研究氯化钠(NaCI)调节商用AH佐剂颗粒悬浮液离子强度的理化效应。x射线光电子能谱数据表明,用NaCI调节I和沉积在金表面都不会改变AH颗粒的表面化学组成。后一个结果提供了使用ah涂层金表面作为辅助颗粒高级表面分析平台的机会,例如通过原子力显微镜(AFM)。通过扫描电镜和原子力显微镜对天然和NaCI处理过的AH悬浮液中回收的佐剂颗粒的形貌进行研究,发现NaCI的加入显著改变了AH颗粒的聚集状态。氮吸附实验进一步证实了这一点:nacl将I调节到150 mM,会强烈促进AH颗粒聚集,导致发育比表面积大幅下降。因此,这项工作证明了NaCI对AH佐剂结构的影响,这可能导致配方疫苗的改变和对佐剂颗粒上抗原吸附相关数据的误解。(C) 2016 Elsevier B.V.版权所有
The immunostimulation capacity of most vaccines is enhanced through antigen adsorption on aluminum hydroxide (AH) adjuvants. Varying the adsorption conditions, i.e. pH and ionic strength (I), changes the antigen adsorbed amount and therefore the ability of the vaccine to stimulate the immune system. Vaccine formulations are thus resulting from an empirical screening of the adsorption conditions. This work aims at studying the physicochemical effects of adjusting the ionic strength of commercial AH adjuvant particles suspensions with sodium chloride (NaCI). X-ray photoelectron spectroscopy data show that AH particles surface chemical composition is neither altered by I adjustment with NaCI nor by deposition on gold surfaces. The latter result provides the opportunity to use AH-coated gold surfaces as a platform for advanced surface analysis of adjuvant particles, e.g. by atomic force microscopy (AFM). The morphology of adjuvant particles recovered from native and NaCI-treated AH suspensions, as studied by scanning electron microscopy and AFM, reveals that AH particles aggregation state is significantly altered by NaCI addition. This is further confirmed by nitrogen adsorption experiments: I adjustment to 150 mM with NaCI strongly promotes AH particles aggregation leading to a strong decrease of the developed specific surface area. This work thus evidences the effect of NaCI on AH adjuvant structure, which may lead to alteration of formulated vaccines and to misinterpretation of data related to antigen adsorption on adjuvant particles. (C) 2016 Elsevier B.V. All rights reserved.