Noges Laura E, White Janice, Cambier John C, Kappler John W, Marrack Philippa
Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; and.
Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
J Immunol. 2016 Aug 15;197(4):1221-30. doi: 10.4049/jimmunol.1501565. Epub 2016 Jun 29.
Aluminum salt (alum) adjuvants have been used for many years as adjuvants for human vaccines because they are safe and effective. Despite its widespread use, the means by which alum acts as an adjuvant remains poorly understood. Recently, it was shown that injected alum is rapidly coated with host chromatin within mice. Experiments suggested that the host DNA in the coating chromatin contributed to alum's adjuvant activity. Some of the experiments used commercially purchased DNase and showed that coinjection of these DNase preparations with alum and Ag reduced the host's immune response to the vaccine. In this study, we report that some commercial DNase preparations are contaminated with proteases. These proteases are responsible for most of the ability of DNase preparations to inhibit alum's adjuvant activity. Nevertheless, DNase somewhat reduces responses to some Ags with alum. The effect of DNase is independent of its ability to cleave DNA, suggesting that alum improves CD4 responses to Ag via a pathway other than host DNA sensing.
铝盐（明矾）佐剂多年来一直被用作人类疫苗的佐剂，因为它们安全有效。尽管其广泛使用，但明矾作为佐剂的作用方式仍知之甚少。最近，研究表明，注射的明矾在小鼠体内会迅速被宿主染色质包裹。实验表明，包裹染色质中的宿主DNA有助于明矾的佐剂活性。一些实验使用了市售的脱氧核糖核酸酶（DNase），结果显示将这些DNase制剂与明矾和抗原（Ag）共同注射会降低宿主对疫苗的免疫反应。在本研究中，我们报告一些市售的DNase制剂被蛋白酶污染。这些蛋白酶是DNase制剂抑制明矾佐剂活性的主要原因。尽管如此，DNase在一定程度上会降低明矾对某些抗原的反应。DNase的作用与其切割DNA的能力无关，这表明明矾通过宿主DNA传感以外的途径改善了对抗原的CD4反应。
