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Distinctive cellular response to aluminum based adjuvants

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 t...

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Autores principales: Nies, Isaac, Hidalgo, Krisha, Bondy, Stephen C., Campbell, Arezoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189866/
https://www.ncbi.nlm.nih.gov/pubmed/32388105
http://dx.doi.org/10.1016/j.etap.2020.103404
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author Nies, Isaac
Hidalgo, Krisha
Bondy, Stephen C.
Campbell, Arezoo
author_facet Nies, Isaac
Hidalgo, Krisha
Bondy, Stephen C.
Campbell, Arezoo
author_sort Nies, Isaac
collection PubMed
description 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.
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spelling pubmed-71898662020-04-29 Distinctive cellular response to aluminum based adjuvants Nies, Isaac Hidalgo, Krisha Bondy, Stephen C. Campbell, Arezoo Environ Toxicol Pharmacol Article 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. Elsevier B.V. 2020-08 2020-04-29 /pmc/articles/PMC7189866/ /pubmed/32388105 http://dx.doi.org/10.1016/j.etap.2020.103404 Text en © 2020 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Nies, Isaac
Hidalgo, Krisha
Bondy, Stephen C.
Campbell, Arezoo
Distinctive cellular response to aluminum based adjuvants
title Distinctive cellular response to aluminum based adjuvants
title_full Distinctive cellular response to aluminum based adjuvants
title_fullStr Distinctive cellular response to aluminum based adjuvants
title_full_unstemmed Distinctive cellular response to aluminum based adjuvants
title_short Distinctive cellular response to aluminum based adjuvants
title_sort distinctive cellular response to aluminum based adjuvants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189866/
https://www.ncbi.nlm.nih.gov/pubmed/32388105
http://dx.doi.org/10.1016/j.etap.2020.103404
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