TY - JOUR

T1 - Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection

AU - Bach, Emil

AU - Fitzgerald, Stephen F.

AU - Williams-MacDonald, Sarah E.

AU - Mitchell, Mairi

AU - Golde, William T.

AU - Longbottom, David

AU - Nisbet, Alasdair J.

AU - Dinkla, Annemieke

AU - Sullivan, Eric

AU - Pinapati, Richard S.

AU - Tan, John C.

AU - Joosten, Leo A.B.

AU - Roest, Hendrik Jan

AU - Østerbye, Thomas

AU - Koets, Ad P.

AU - Buus, Søren

AU - McNeilly, Tom N.

N1 - Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Department of Health and Social Care using UK Aid funding and is managed by the BBSRC (BB/R019975/1). The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health and Social Care. The funding bodies had no role in the study design, data collection, and interpretation or the decision to submit the work for publication. Publisher Copyright: Copyright © 2023 Bach, Fitzgerald, Williams-MacDonald, Mitchell, Golde, Longbottom, Nisbet, Dinkla, Sullivan, Pinapati, Tan, Joosten, Roest, Østerbye, Koets, Buus and McNeilly.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - B cell epitope mapping

KW - Coxiella burnetii

KW - peptide microarray

KW - Q fever

KW - serodiagnostic

KW - vaccination

U2 - 10.3389/fimmu.2023.1257722

DO - 10.3389/fimmu.2023.1257722

M3 - Journal article

C2 - 37954609

AN - SCOPUS:85176771531

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1257722

ER -