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Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route

Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the availability of appropriate animal models for eff...

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Autores principales: Johnston, Sara C., Wilhelmsen, Catherine L., Shamblin, Joshua, Kimmel, Adrienne, Zelko, Justine, Wollen, Suzanne, Goff, Arthur J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415412/
https://www.ncbi.nlm.nih.gov/pubmed/34484210
http://dx.doi.org/10.3389/fimmu.2021.709772
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author Johnston, Sara C.
Wilhelmsen, Catherine L.
Shamblin, Joshua
Kimmel, Adrienne
Zelko, Justine
Wollen, Suzanne
Goff, Arthur J.
author_facet Johnston, Sara C.
Wilhelmsen, Catherine L.
Shamblin, Joshua
Kimmel, Adrienne
Zelko, Justine
Wollen, Suzanne
Goff, Arthur J.
author_sort Johnston, Sara C.
collection PubMed
description Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the availability of appropriate animal models for efficacy evaluations. The most commonly used nonhuman primate models for efficacy evaluations against Ebola virus utilize the intramuscular or aerosol route of exposure. Although clinical disease signs are similar to human cases, disease progression in these models is much more rapid, and this can pose significant hurdles for countermeasure evaluations. The objective of the present study was to evaluate the Ebola virus disease course that arises after cynomolgus macaques are exposed to Ebola virus by a mucosal route (the intranasal route). Two different doses (10 pfu and 100 pfu) and delivery methodologies (drop-wise and mucosal atomization device) were evaluated on this study. Differences in clinical disease between dose and delivery groups were not noted. However, a delayed disease course was identified for approximately half of the animals on study, and this delayed disease was dose and administration method independent. Therefore, it appears that mucosal exposure with Ebola virus results in a disease course in cynomolgus macaques that more accurately replicates that which is documented for human cases. In summary, the data presented support the need for further development of this model as a possible alternative to parenteral and small-particle aerosol models for the study of human Ebola virus disease and for countermeasure evaluations.
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spelling pubmed-84154122021-09-04 Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route Johnston, Sara C. Wilhelmsen, Catherine L. Shamblin, Joshua Kimmel, Adrienne Zelko, Justine Wollen, Suzanne Goff, Arthur J. Front Immunol Immunology Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the availability of appropriate animal models for efficacy evaluations. The most commonly used nonhuman primate models for efficacy evaluations against Ebola virus utilize the intramuscular or aerosol route of exposure. Although clinical disease signs are similar to human cases, disease progression in these models is much more rapid, and this can pose significant hurdles for countermeasure evaluations. The objective of the present study was to evaluate the Ebola virus disease course that arises after cynomolgus macaques are exposed to Ebola virus by a mucosal route (the intranasal route). Two different doses (10 pfu and 100 pfu) and delivery methodologies (drop-wise and mucosal atomization device) were evaluated on this study. Differences in clinical disease between dose and delivery groups were not noted. However, a delayed disease course was identified for approximately half of the animals on study, and this delayed disease was dose and administration method independent. Therefore, it appears that mucosal exposure with Ebola virus results in a disease course in cynomolgus macaques that more accurately replicates that which is documented for human cases. In summary, the data presented support the need for further development of this model as a possible alternative to parenteral and small-particle aerosol models for the study of human Ebola virus disease and for countermeasure evaluations. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415412/ /pubmed/34484210 http://dx.doi.org/10.3389/fimmu.2021.709772 Text en Copyright © 2021 Johnston, Wilhelmsen, Shamblin, Kimmel, Zelko, Wollen and Goff https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Johnston, Sara C.
Wilhelmsen, Catherine L.
Shamblin, Joshua
Kimmel, Adrienne
Zelko, Justine
Wollen, Suzanne
Goff, Arthur J.
Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route
title Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route
title_full Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route
title_fullStr Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route
title_full_unstemmed Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route
title_short Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route
title_sort delayed disease in cynomolgus macaques exposed to ebola virus by an intranasal route
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415412/
https://www.ncbi.nlm.nih.gov/pubmed/34484210
http://dx.doi.org/10.3389/fimmu.2021.709772
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