Contamination of DNase Preparations Confounds Analysis of the Role of DNA in Alum-Adjuvanted Vaccines

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 c...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2016-08, Vol.197 (4), p.1221-1230
Main Authors: Noges, Laura E, White, Janice, Cambier, John C, Kappler, John W, Marrack, Philippa
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Alum Compounds - pharmacology
Animals
Antigens - immunology
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - drug effects
CD8-Positive T-Lymphocytes - immunology
Deoxyribonucleases - chemistry
Deoxyribonucleases - immunology
Deoxyribonucleases - pharmacology
DNA - immunology
Drug Contamination
Enzyme-Linked Immunosorbent Assay
Female
Immunotherapy and Vaccines
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Mass Spectrometry
Mice
Mice, Inbred C57BL
Vaccines - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1501565