Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep

The use of vaccines including aluminum (Al)–based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injection-site granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P < .001) in the lymph nodes of the vaccine group (82.65 μg/g) compared with both adjuvant-only (2.53 μg/g) and control groups (0.96 μg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs.

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Main Authors: Asín, Javier, Molín, Jéssica, Pérez, Marta M., Pinczowski, Pedro, Gimeno, Marina, Navascués, Nuria, Muniesa, Ana, Blas, Ignacio de, Lacasta, Delia, Fernández, Antonio, Pablo, Lorena de, Mold, Matthew, Exley, Christopher, Andrés, Damián F. de, Reina, Ramsés, Luján, Lluís
Other Authors: Mold, Matthew [0000-0002-4616-6204]
Format: artículo biblioteca
Language:English
Published: Sage Publications 2019
Subjects:Aluminum-based adjuvants, Granuloma, Macrophage, Sheep, Lymph node, Vaccine,
Online Access:http://hdl.handle.net/10261/191869
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spelling dig-idab-es-10261-1918692020-04-16T07:10:42Z Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep Asín, Javier Molín, Jéssica Pérez, Marta M. Pinczowski, Pedro Gimeno, Marina Navascués, Nuria Muniesa, Ana Blas, Ignacio de Lacasta, Delia Fernández, Antonio Pablo, Lorena de Mold, Matthew Exley, Christopher Andrés, Damián F. de Reina, Ramsés Luján, Lluís Mold, Matthew [0000-0002-4616-6204] Luján, Lluís [0000-0002-2053-9842] Aluminum-based adjuvants Granuloma Macrophage Sheep Lymph node Vaccine The use of vaccines including aluminum (Al)–based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injection-site granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P < .001) in the lymph nodes of the vaccine group (82.65 μg/g) compared with both adjuvant-only (2.53 μg/g) and control groups (0.96 μg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs. Peer reviewed 2019-09-30T11:39:53Z 2019-09-30T11:39:53Z 2019 artículo http://purl.org/coar/resource_type/c_6501 Veterinary Pathology 56(3): 418–428 (2019) 1865-1674 0300-9858 http://hdl.handle.net/10261/191869 10.1177/0300985818809142 1544-2217 en https://doi.org/10.1177/0300985818809142 Sí none Sage Publications
institution IDAB ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-idab-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del IDAB España
language English
topic Aluminum-based adjuvants
Granuloma
Macrophage
Sheep
Lymph node
Vaccine
Aluminum-based adjuvants
Granuloma
Macrophage
Sheep
Lymph node
Vaccine
spellingShingle Aluminum-based adjuvants
Granuloma
Macrophage
Sheep
Lymph node
Vaccine
Aluminum-based adjuvants
Granuloma
Macrophage
Sheep
Lymph node
Vaccine
Asín, Javier
Molín, Jéssica
Pérez, Marta M.
Pinczowski, Pedro
Gimeno, Marina
Navascués, Nuria
Muniesa, Ana
Blas, Ignacio de
Lacasta, Delia
Fernández, Antonio
Pablo, Lorena de
Mold, Matthew
Exley, Christopher
Andrés, Damián F. de
Reina, Ramsés
Luján, Lluís
Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep
description The use of vaccines including aluminum (Al)–based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injection-site granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P < .001) in the lymph nodes of the vaccine group (82.65 μg/g) compared with both adjuvant-only (2.53 μg/g) and control groups (0.96 μg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs.
author2 Mold, Matthew [0000-0002-4616-6204]
author_facet Mold, Matthew [0000-0002-4616-6204]
Asín, Javier
Molín, Jéssica
Pérez, Marta M.
Pinczowski, Pedro
Gimeno, Marina
Navascués, Nuria
Muniesa, Ana
Blas, Ignacio de
Lacasta, Delia
Fernández, Antonio
Pablo, Lorena de
Mold, Matthew
Exley, Christopher
Andrés, Damián F. de
Reina, Ramsés
Luján, Lluís
format artículo
topic_facet Aluminum-based adjuvants
Granuloma
Macrophage
Sheep
Lymph node
Vaccine
author Asín, Javier
Molín, Jéssica
Pérez, Marta M.
Pinczowski, Pedro
Gimeno, Marina
Navascués, Nuria
Muniesa, Ana
Blas, Ignacio de
Lacasta, Delia
Fernández, Antonio
Pablo, Lorena de
Mold, Matthew
Exley, Christopher
Andrés, Damián F. de
Reina, Ramsés
Luján, Lluís
author_sort Asín, Javier
title Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep
title_short Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep
title_full Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep
title_fullStr Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep
title_full_unstemmed Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep
title_sort granulomas following subcutaneous injection with aluminum adjuvant-containing products in sheep
publisher Sage Publications
publishDate 2019
url http://hdl.handle.net/10261/191869
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