Aluminum-based adjuvants (ABAs) are used in human vaccines to enhance the magnitude of protective immune responses elicited against specific pathogens. One hypothesis is that stress signals released by aluminum-exposed necrotic cells play a role in modulating an immune response that contributes to the adjuvant’s effectiveness. We hypothesized that aluminum adjuvant-induced necrosis would be similar irrespective of cellular origin or composition of the adjuvant. To test this hypothesis, human macrophages derived from peripheral monocytic cell line (THP-1) and cells derived from the human brain (primary astrocytes) were evaluated. Three commercially available formulations of ABAs (Alhydrogel, Imject alum, and Adju-Phos) were examined. Alum was also used as a reference. Cell viability, reactive oxygen species formation, and production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were quantified. Cells were exposed to different concentrations (10−100 μg/mL) of the adjuvants for 24 h or 72 h. The two FDA approved adjuvants (Alhydrogel and Adju-Phos) decreased cell viability in both cell types. At the 72 h time point, the decrease in viability was accompanied with increased ROS formation. The size of the aluminum agglomerates was not relatable to the changes observed. After exposure to ABAs, astrocytes and macrophages presented a distinct profile of cytokine secretion which may relate to the function and unique characteristics of each cell type. These variations indicate that aluminum adjuvants may have differing capability of activating cells of different origin and thus their utility in specific vaccine design should be carefully assessed for optimum efficacy.

铝基佐剂（ABA）用于人类疫苗中，以增强针对特定病原体的保护性免疫应答的强度。一种假设是，暴露于铝的坏死细胞释放的应激信号在调节免疫应答中起作用，该免疫应答有助于佐剂的有效性。我们假设铝佐剂引起的坏死与细胞起源或佐剂的组成无关。为了验证这一假设，对源自外周单核细胞系（THP-1）的人类巨噬细胞和源自人脑的细胞（原代星形胶质细胞）进行了评估。检查了三种ABA的市售制剂（水凝胶，Imject明矾和Adju-Phos）。明矾也被用作参考。细胞活力，活性氧的形成 量化肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）的产生。将细胞暴露于不同浓度（10-100μg/ mL）的佐剂中24 h或72 h。两种FDA批准的佐剂（Alhydrogel和Adju-Phos）在两种细胞类型中均降低了细胞活力。在72小时的时间点，活力的降低伴随着ROS形成的增加。铝附聚物的尺寸与观察到的变化无关。暴露于ABA后，星形胶质细胞和巨噬细胞呈现出不同的细胞因子分泌特征，这可能与每种细胞类型的功能和独特特征有关。