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Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation

The development of therapies targeted to improve the health of women has utilized direct vaginal delivery as a more effective and less toxic method of protection from HIV and other pathogens. Vaginal applicants and delivery devices that provide sustained effects have been met with increasing accepta...

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Autores principales: Pyles, Richard B., Miller, Aaron L., Maxwell, Carrie, Dawson, Lauren, Richardson-Harman, Nicola, Swartz, Glenn, O'Neill, Cynthia, Walker, Cattlena, Milligan, Gregg N., Madsen, Timothy, Motamedi, Massoud, Vargas, Gracie, Vincent, Kathleen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580801/
https://www.ncbi.nlm.nih.gov/pubmed/36303974
http://dx.doi.org/10.3389/frph.2021.714829
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author Pyles, Richard B.
Miller, Aaron L.
Maxwell, Carrie
Dawson, Lauren
Richardson-Harman, Nicola
Swartz, Glenn
O'Neill, Cynthia
Walker, Cattlena
Milligan, Gregg N.
Madsen, Timothy
Motamedi, Massoud
Vargas, Gracie
Vincent, Kathleen L.
author_facet Pyles, Richard B.
Miller, Aaron L.
Maxwell, Carrie
Dawson, Lauren
Richardson-Harman, Nicola
Swartz, Glenn
O'Neill, Cynthia
Walker, Cattlena
Milligan, Gregg N.
Madsen, Timothy
Motamedi, Massoud
Vargas, Gracie
Vincent, Kathleen L.
author_sort Pyles, Richard B.
collection PubMed
description The development of therapies targeted to improve the health of women has utilized direct vaginal delivery as a more effective and less toxic method of protection from HIV and other pathogens. Vaginal applicants and delivery devices that provide sustained effects have been met with increasing acceptability, but the efficacy and toxicity outcomes have not been successfully predicted by preclinical in vitro studies and animal modeling. We have explored the utilization of sheep as a model for testing the safety of vaginal applicants and devices based on spatial and structural similarities to the human vagina. As recently noted by the FDA, an additional safety measure is an impact on the vaginal microbiome (VMB) that is known to contribute to vaginal health and influence pathogen susceptibility and drug metabolism. To advance the utility of the sheep vaginal model, we completed a thorough molecular characterization of the ovine VMB utilizing both next-generation sequencing (NGS) and PCR methods. The process also created a custom PCR array to quantify ovine VMB community profiles in an affordable, higher throughput fashion. The results from vaginal swabs (>475 samples) collected from non-pregnant crossbred Dorset and Merino ewes treated with selected vaginal applicants or collected as sham samples established 16 VMB community types (VMB CTs). To associate VMB CTs with eubiosis or dysbiosis, we also completed custom ELISAs for six cytokines identifying IL1B, IL8, TNFa, and CXCL10 as useful markers to support the characterization of ovine vaginal inflammation. The results indicated that Pasteurella, Actinobacillus, Pseudomonas, Bacteroides, Leptotrichia, and E. coli were common markers of eubiosis (low inflammatory marker expression), and that Haemophilus, Ureaplasma, and Corynebacterium were associated with dysbiosis (high cytokine levels). Utilizing the optimized workflow, we also confirmed the utility of three commonly used vaginal applicants for impact on the VMB and inflammatory state, producing a dataset that supports the recommendation for the use of sheep for testing of vaginal applicants and devices as part of preclinical pipelines.
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spelling pubmed-95808012022-10-26 Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation Pyles, Richard B. Miller, Aaron L. Maxwell, Carrie Dawson, Lauren Richardson-Harman, Nicola Swartz, Glenn O'Neill, Cynthia Walker, Cattlena Milligan, Gregg N. Madsen, Timothy Motamedi, Massoud Vargas, Gracie Vincent, Kathleen L. Front Reprod Health Reproductive Health The development of therapies targeted to improve the health of women has utilized direct vaginal delivery as a more effective and less toxic method of protection from HIV and other pathogens. Vaginal applicants and delivery devices that provide sustained effects have been met with increasing acceptability, but the efficacy and toxicity outcomes have not been successfully predicted by preclinical in vitro studies and animal modeling. We have explored the utilization of sheep as a model for testing the safety of vaginal applicants and devices based on spatial and structural similarities to the human vagina. As recently noted by the FDA, an additional safety measure is an impact on the vaginal microbiome (VMB) that is known to contribute to vaginal health and influence pathogen susceptibility and drug metabolism. To advance the utility of the sheep vaginal model, we completed a thorough molecular characterization of the ovine VMB utilizing both next-generation sequencing (NGS) and PCR methods. The process also created a custom PCR array to quantify ovine VMB community profiles in an affordable, higher throughput fashion. The results from vaginal swabs (>475 samples) collected from non-pregnant crossbred Dorset and Merino ewes treated with selected vaginal applicants or collected as sham samples established 16 VMB community types (VMB CTs). To associate VMB CTs with eubiosis or dysbiosis, we also completed custom ELISAs for six cytokines identifying IL1B, IL8, TNFa, and CXCL10 as useful markers to support the characterization of ovine vaginal inflammation. The results indicated that Pasteurella, Actinobacillus, Pseudomonas, Bacteroides, Leptotrichia, and E. coli were common markers of eubiosis (low inflammatory marker expression), and that Haemophilus, Ureaplasma, and Corynebacterium were associated with dysbiosis (high cytokine levels). Utilizing the optimized workflow, we also confirmed the utility of three commonly used vaginal applicants for impact on the VMB and inflammatory state, producing a dataset that supports the recommendation for the use of sheep for testing of vaginal applicants and devices as part of preclinical pipelines. Frontiers Media S.A. 2021-12-07 /pmc/articles/PMC9580801/ /pubmed/36303974 http://dx.doi.org/10.3389/frph.2021.714829 Text en Copyright © 2021 Pyles, Miller, Maxwell, Dawson, Richardson-Harman, Swartz, O'Neill, Walker, Milligan, Madsen, Motamedi, Vargas and Vincent. 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 Reproductive Health
Pyles, Richard B.
Miller, Aaron L.
Maxwell, Carrie
Dawson, Lauren
Richardson-Harman, Nicola
Swartz, Glenn
O'Neill, Cynthia
Walker, Cattlena
Milligan, Gregg N.
Madsen, Timothy
Motamedi, Massoud
Vargas, Gracie
Vincent, Kathleen L.
Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation
title Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation
title_full Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation
title_fullStr Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation
title_full_unstemmed Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation
title_short Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation
title_sort characterization of the ovine vaginal microbiome and inflammation patterns as an improved testing model of human vaginal irritation
topic Reproductive Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580801/
https://www.ncbi.nlm.nih.gov/pubmed/36303974
http://dx.doi.org/10.3389/frph.2021.714829
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