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Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection
Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of human infection. Vaccination is a key control measure, and two comm...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637584/ https://www.ncbi.nlm.nih.gov/pubmed/37954609 http://dx.doi.org/10.3389/fimmu.2023.1257722 |
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author | Bach, Emil Fitzgerald, Stephen F. Williams-MacDonald, Sarah E. Mitchell, Mairi Golde, William T. Longbottom, David Nisbet, Alasdair J. Dinkla, Annemieke Sullivan, Eric Pinapati, Richard S. Tan, John C. Joosten, Leo A. B. Roest, Hendrik-Jan Østerbye, Thomas Koets, Ad P. Buus, Søren McNeilly, Tom N. |
author_facet | Bach, Emil Fitzgerald, Stephen F. Williams-MacDonald, Sarah E. Mitchell, Mairi Golde, William T. Longbottom, David Nisbet, Alasdair J. Dinkla, Annemieke Sullivan, Eric Pinapati, Richard S. Tan, John C. Joosten, Leo A. B. Roest, Hendrik-Jan Østerbye, Thomas Koets, Ad P. Buus, Søren McNeilly, Tom N. |
author_sort | Bach, Emil |
collection | PubMed |
description | Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of human infection. Vaccination is a key control measure, and two commercial vaccines based on formalin-inactivated C. burnetii bacterins are currently available for use in livestock and humans. However, their deployment is limited due to significant reactogenicity in individuals previously sensitized to C. burnetii antigens. Furthermore, these vaccines interfere with available serodiagnostic tests which are also based on C. burnetii bacterin antigens. Defined subunit antigen vaccines offer significant advantages, as they can be engineered to reduce reactogenicity and co-designed with serodiagnostic tests to allow discrimination between vaccinated and infected individuals. This study aimed to investigate the diversity of antibody responses to C. burnetii vaccination and/or infection in cattle, goats, humans, and sheep through genome-wide linear epitope mapping to identify candidate vaccine and diagnostic antigens within the predicted bacterial proteome. Using high-density peptide microarrays, we analyzed the seroreactivity in 156 serum samples from vaccinated and infected individuals to peptides derived from 2,092 open-reading frames in the C. burnetii genome. We found significant diversity in the antibody responses within and between species and across different types of C. burnetii exposure. Through the implementation of three different vaccine candidate selection methods, we identified 493 candidate protein antigens for protein subunit vaccine design or serodiagnostic evaluation, of which 65 have been previously described. This is the first study to investigate multi-species seroreactivity against the entire C. burnetii proteome presented as overlapping linear peptides and provides the basis for the selection of antigen targets for next-generation Q fever vaccines and diagnostic tests. |
format | Online Article Text |
id | pubmed-10637584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106375842023-11-11 Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection Bach, Emil Fitzgerald, Stephen F. Williams-MacDonald, Sarah E. Mitchell, Mairi Golde, William T. Longbottom, David Nisbet, Alasdair J. Dinkla, Annemieke Sullivan, Eric Pinapati, Richard S. Tan, John C. Joosten, Leo A. B. Roest, Hendrik-Jan Østerbye, Thomas Koets, Ad P. Buus, Søren McNeilly, Tom N. Front Immunol Immunology Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of human infection. Vaccination is a key control measure, and two commercial vaccines based on formalin-inactivated C. burnetii bacterins are currently available for use in livestock and humans. However, their deployment is limited due to significant reactogenicity in individuals previously sensitized to C. burnetii antigens. Furthermore, these vaccines interfere with available serodiagnostic tests which are also based on C. burnetii bacterin antigens. Defined subunit antigen vaccines offer significant advantages, as they can be engineered to reduce reactogenicity and co-designed with serodiagnostic tests to allow discrimination between vaccinated and infected individuals. This study aimed to investigate the diversity of antibody responses to C. burnetii vaccination and/or infection in cattle, goats, humans, and sheep through genome-wide linear epitope mapping to identify candidate vaccine and diagnostic antigens within the predicted bacterial proteome. Using high-density peptide microarrays, we analyzed the seroreactivity in 156 serum samples from vaccinated and infected individuals to peptides derived from 2,092 open-reading frames in the C. burnetii genome. We found significant diversity in the antibody responses within and between species and across different types of C. burnetii exposure. Through the implementation of three different vaccine candidate selection methods, we identified 493 candidate protein antigens for protein subunit vaccine design or serodiagnostic evaluation, of which 65 have been previously described. This is the first study to investigate multi-species seroreactivity against the entire C. burnetii proteome presented as overlapping linear peptides and provides the basis for the selection of antigen targets for next-generation Q fever vaccines and diagnostic tests. Frontiers Media S.A. 2023-10-26 /pmc/articles/PMC10637584/ /pubmed/37954609 http://dx.doi.org/10.3389/fimmu.2023.1257722 Text en Copyright © 2023 Bach, Fitzgerald, Williams-MacDonald, Mitchell, Golde, Longbottom, Nisbet, Dinkla, Sullivan, Pinapati, Tan, Joosten, Roest, Østerbye, Koets, Buus and McNeilly 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 Bach, Emil Fitzgerald, Stephen F. Williams-MacDonald, Sarah E. Mitchell, Mairi Golde, William T. Longbottom, David Nisbet, Alasdair J. Dinkla, Annemieke Sullivan, Eric Pinapati, Richard S. Tan, John C. Joosten, Leo A. B. Roest, Hendrik-Jan Østerbye, Thomas Koets, Ad P. Buus, Søren McNeilly, Tom N. Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection |
title | Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection |
title_full | Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection |
title_fullStr | Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection |
title_full_unstemmed | Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection |
title_short | Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection |
title_sort | genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to coxiella burnetii vaccination and infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637584/ https://www.ncbi.nlm.nih.gov/pubmed/37954609 http://dx.doi.org/10.3389/fimmu.2023.1257722 |
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