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Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi

Immune correlates of protection against intracellular bacterial pathogens are largely thought to be cell-mediated, although a reasonable amount of data supports a role for antibody-mediated protection. To define a role for antibody-mediated immunity against an intracellular pathogen, Rhodococcus equ...

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Autores principales: Cywes-Bentley, Colette, Rocha, Joana N., Bordin, Angela I., Vinacur, Mariana, Rehman, Safia, Zaidi, Tanweer S., Meyer, Mark, Anthony, Sarah, Lambert, McKenzie, Vlock, Daniel R., Giguère, Steeve, Cohen, Noah D., Pier, Gerald B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053243/
https://www.ncbi.nlm.nih.gov/pubmed/30024986
http://dx.doi.org/10.1371/journal.ppat.1007160
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author Cywes-Bentley, Colette
Rocha, Joana N.
Bordin, Angela I.
Vinacur, Mariana
Rehman, Safia
Zaidi, Tanweer S.
Meyer, Mark
Anthony, Sarah
Lambert, McKenzie
Vlock, Daniel R.
Giguère, Steeve
Cohen, Noah D.
Pier, Gerald B.
author_facet Cywes-Bentley, Colette
Rocha, Joana N.
Bordin, Angela I.
Vinacur, Mariana
Rehman, Safia
Zaidi, Tanweer S.
Meyer, Mark
Anthony, Sarah
Lambert, McKenzie
Vlock, Daniel R.
Giguère, Steeve
Cohen, Noah D.
Pier, Gerald B.
author_sort Cywes-Bentley, Colette
collection PubMed
description Immune correlates of protection against intracellular bacterial pathogens are largely thought to be cell-mediated, although a reasonable amount of data supports a role for antibody-mediated protection. To define a role for antibody-mediated immunity against an intracellular pathogen, Rhodococcus equi, that causes granulomatous pneumonia in horse foals, we devised and tested an experimental system relying solely on antibody-mediated protection against this host-specific etiologic agent. Immunity was induced by vaccinating pregnant mares 6 and 3 weeks prior to predicted parturition with a conjugate vaccine targeting the highly conserved microbial surface polysaccharide, poly-N-acetyl glucosamine (PNAG). We ascertained antibody was transferred to foals via colostrum, the only means for foals to acquire maternal antibody. Horses lack transplacental antibody transfer. Next, a randomized, controlled, blinded challenge was conducted by inoculating at ~4 weeks of age ~10(6) cfu of R. equi via intrabronchial challenge. Eleven of 12 (91%) foals born to immune mares did not develop clinical R. equi pneumonia, whereas 6 of 7 (86%) foals born to unvaccinated controls developed pneumonia (P = 0.0017). In a confirmatory passive immunization study, infusion of PNAG-hyperimmune plasma protected 100% of 5 foals against R. equi pneumonia whereas all 4 recipients of normal horse plasma developed clinical disease (P = 0.0079). Antibodies to PNAG mediated killing of extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms depended on antibody recognition of surface expression of PNAG on infected cells, along with complement deposition and PMN-assisted lysis of infected macrophages. Peripheral blood mononuclear cells from immune and protected foals released higher levels of interferon-γ in response to PNAG compared to controls, indicating vaccination also induced an antibody-dependent cellular release of this critical immune cytokine. Overall, antibody-mediated opsonic killing and interferon-γ release in response to PNAG may protect against diseases caused by intracellular bacterial pathogens.
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spelling pubmed-60532432018-07-27 Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi Cywes-Bentley, Colette Rocha, Joana N. Bordin, Angela I. Vinacur, Mariana Rehman, Safia Zaidi, Tanweer S. Meyer, Mark Anthony, Sarah Lambert, McKenzie Vlock, Daniel R. Giguère, Steeve Cohen, Noah D. Pier, Gerald B. PLoS Pathog Research Article Immune correlates of protection against intracellular bacterial pathogens are largely thought to be cell-mediated, although a reasonable amount of data supports a role for antibody-mediated protection. To define a role for antibody-mediated immunity against an intracellular pathogen, Rhodococcus equi, that causes granulomatous pneumonia in horse foals, we devised and tested an experimental system relying solely on antibody-mediated protection against this host-specific etiologic agent. Immunity was induced by vaccinating pregnant mares 6 and 3 weeks prior to predicted parturition with a conjugate vaccine targeting the highly conserved microbial surface polysaccharide, poly-N-acetyl glucosamine (PNAG). We ascertained antibody was transferred to foals via colostrum, the only means for foals to acquire maternal antibody. Horses lack transplacental antibody transfer. Next, a randomized, controlled, blinded challenge was conducted by inoculating at ~4 weeks of age ~10(6) cfu of R. equi via intrabronchial challenge. Eleven of 12 (91%) foals born to immune mares did not develop clinical R. equi pneumonia, whereas 6 of 7 (86%) foals born to unvaccinated controls developed pneumonia (P = 0.0017). In a confirmatory passive immunization study, infusion of PNAG-hyperimmune plasma protected 100% of 5 foals against R. equi pneumonia whereas all 4 recipients of normal horse plasma developed clinical disease (P = 0.0079). Antibodies to PNAG mediated killing of extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms depended on antibody recognition of surface expression of PNAG on infected cells, along with complement deposition and PMN-assisted lysis of infected macrophages. Peripheral blood mononuclear cells from immune and protected foals released higher levels of interferon-γ in response to PNAG compared to controls, indicating vaccination also induced an antibody-dependent cellular release of this critical immune cytokine. Overall, antibody-mediated opsonic killing and interferon-γ release in response to PNAG may protect against diseases caused by intracellular bacterial pathogens. Public Library of Science 2018-07-19 /pmc/articles/PMC6053243/ /pubmed/30024986 http://dx.doi.org/10.1371/journal.ppat.1007160 Text en © 2018 Cywes-Bentley et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cywes-Bentley, Colette
Rocha, Joana N.
Bordin, Angela I.
Vinacur, Mariana
Rehman, Safia
Zaidi, Tanweer S.
Meyer, Mark
Anthony, Sarah
Lambert, McKenzie
Vlock, Daniel R.
Giguère, Steeve
Cohen, Noah D.
Pier, Gerald B.
Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi
title Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi
title_full Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi
title_fullStr Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi
title_full_unstemmed Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi
title_short Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi
title_sort antibody to poly-n-acetyl glucosamine provides protection against intracellular pathogens: mechanism of action and validation in horse foals challenged with rhodococcus equi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053243/
https://www.ncbi.nlm.nih.gov/pubmed/30024986
http://dx.doi.org/10.1371/journal.ppat.1007160
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