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<p>Aluminum adjuvants are the most common adjuvants in human vaccines. The two types of aluminum adjuvants, aluminum hydroxide adjuvant (AH) and aluminum phosphate adjuvant (AP), differ in physical and chemical characteristics, but little is known about possible biological differences. While previous work demonstrated that AH and AP induce the secretion of IL-1β in an NLRP3-dependent manner, the role of NLRP3 in the stimulation of the immune response by aluminum adjuvants is controversial. Here, we report that AP induces more IL-1β in human and mouse macrophages and dendritic cells than AH. This effect is caused by increased NLRP3-dependent proteolysis of pro-IL-1β. In addition, AP caused a greater degree of cell damage than AH, resulting in the release of lactate dehydrogenase (LDH) and pro-IL-1β. The cell damage caused by aluminum adjuvants was partially dependent on NLRP3, suggesting that pyroptosis and other mechanisms of cell death are involved. In spite of these differences in NLRP3-dependent production of IL-1β, the ability of both aluminum adjuvants to enhance the antibody response in two different mouse models was not affected by deletion or inhibition of NLRP3. These results support the concept that aluminum adjuvants elicit redundant innate immune mechanisms that result in an enhanced adaptive immune response.</p>

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Aluminum adjuvants differentially induce IL-1β release in vitro yet share NLRP3 inflammasome-independent adjuvant effects in vivo

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月10日

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  • Daniela Castillo Perez,
  • Juan F. Hernandez-Franco,
  • Harm HogenEsch

摘要

Aluminum adjuvants are the most common adjuvants in human vaccines. The two types of aluminum adjuvants, aluminum hydroxide adjuvant (AH) and aluminum phosphate adjuvant (AP), differ in physical and chemical characteristics, but little is known about possible biological differences. While previous work demonstrated that AH and AP induce the secretion of IL-1β in an NLRP3-dependent manner, the role of NLRP3 in the stimulation of the immune response by aluminum adjuvants is controversial. Here, we report that AP induces more IL-1β in human and mouse macrophages and dendritic cells than AH. This effect is caused by increased NLRP3-dependent proteolysis of pro-IL-1β. In addition, AP caused a greater degree of cell damage than AH, resulting in the release of lactate dehydrogenase (LDH) and pro-IL-1β. The cell damage caused by aluminum adjuvants was partially dependent on NLRP3, suggesting that pyroptosis and other mechanisms of cell death are involved. In spite of these differences in NLRP3-dependent production of IL-1β, the ability of both aluminum adjuvants to enhance the antibody response in two different mouse models was not affected by deletion or inhibition of NLRP3. These results support the concept that aluminum adjuvants elicit redundant innate immune mechanisms that result in an enhanced adaptive immune response.