title: Contamination of DNase Preparations Confounds Analysis of the Role of DNA in Alum-Adjuvanted Vaccines.
abstract: 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.
authors.affiliation: 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.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Noges
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Janice
authors.initials: J
authors.lastname: White
authors.affiliation: 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.
authors.forename: John C
authors.identifier: 0000-0002-7803-242X
authors.initials: JC
authors.lastname: Cambier
authors.affiliation: 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 Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206.
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.affiliation: 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 Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206 marrackp@njhealth.org.
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004247:DNA / Q000276:immunology; D003851:Deoxyribonucleases / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D004340:Drug Contamination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; D014612:Vaccines; C041524:aluminum sulfate; D004247:DNA; D003851:Deoxyribonucleases