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Coxiella burnetii epitope-specific T-cell responses in chronic Q fever patients

Anja Scholzen, Guilhem Richard, Leonard Moise, Eva Hartman, Chantal P. Bleeker-Rovers, Patrick M. Reeves, Susan Raju Paul, William D. Martin, Anne S. De Groot, Mark C. Poznansky, Ann E. Sluder, Anja Garritsen
doi: https://doi.org/10.1101/582007
Anja Scholzen
1InnatOss Laboratories B.V., Oss, Netherlands
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  • For correspondence: anja.scholzen@innatoss.com asluder@mgh.harvard.edu anja.garritsen@innatoss.com
Guilhem Richard
2EpiVax, Inc., Providence, Rhode Island, United States of America
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Leonard Moise
2EpiVax, Inc., Providence, Rhode Island, United States of America
3Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, Rhode Island, United States of America
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Eva Hartman
1InnatOss Laboratories B.V., Oss, Netherlands
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Chantal P. Bleeker-Rovers
4Radboud Expertise Center for Q Fever, Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands
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Patrick M. Reeves
5Massachusetts General Hospital, Vaccine and Immunotherapy Center, Boston, Massachusetts, United States of America
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Susan Raju Paul
5Massachusetts General Hospital, Vaccine and Immunotherapy Center, Boston, Massachusetts, United States of America
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William D. Martin
2EpiVax, Inc., Providence, Rhode Island, United States of America
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Anne S. De Groot
2EpiVax, Inc., Providence, Rhode Island, United States of America
3Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, Rhode Island, United States of America
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Mark C. Poznansky
5Massachusetts General Hospital, Vaccine and Immunotherapy Center, Boston, Massachusetts, United States of America
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Ann E. Sluder
5Massachusetts General Hospital, Vaccine and Immunotherapy Center, Boston, Massachusetts, United States of America
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  • For correspondence: anja.scholzen@innatoss.com asluder@mgh.harvard.edu anja.garritsen@innatoss.com
Anja Garritsen
1InnatOss Laboratories B.V., Oss, Netherlands
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  • For correspondence: anja.scholzen@innatoss.com asluder@mgh.harvard.edu anja.garritsen@innatoss.com
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Abstract

Infection with Coxiella burnetii, the causative agent of Q fever, can result in life-threatening persistent infection. Reactogenicity hinders worldwide implementation of the only licensed human Q fever vaccine. We previously demonstrated long-lived immunoreactivity in individuals with past symptomatic and asymptomatic Coxiella infection (convalescents) to promiscuous HLA-class II C. burnetii epitopes, providing the basis for a novel T-cell-targeted subunit vaccine. Here we investigated in a cohort of 22 individuals with persistent infection (chronic Q fever) whether they recognize the same set of epitopes, or distinct epitopes that could be candidates for a therapeutic vaccine or aid in the diagnosis of persistent infection.

Individuals with chronic Q fever showed strong class II epitope-specific cultured ELISpot responses largely overlapping with the peptide repertoire identified previously for convalescents. Five additional peptides were recognized more frequently by chronic subjects, but there was no combination of epitopes uniquely recognized by or non-reactive in chronic Q fever subjects. Consistent with more recent/prolonged exposure, we found, however, stronger direct ex vivo responses to whole-cell C. burnetii and individual peptides in direct ELISpot than in convalescents.

In conclusion, we have validated and expanded a previously published set candidate epitopes for a novel T-cell targeted subunit Q fever vaccine in the context of chronic Q fever patients and demonstrated that they successfully mounted a T-cell response comparable to that of convalescents. Finally, we demonstrate that individuals treated for chronic Q fever mount a broader ex vivo response to class II epitopes than convalescents, which could be explored for diagnostic purposes.

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Posted March 20, 2019.
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Coxiella burnetii epitope-specific T-cell responses in chronic Q fever patients
Anja Scholzen, Guilhem Richard, Leonard Moise, Eva Hartman, Chantal P. Bleeker-Rovers, Patrick M. Reeves, Susan Raju Paul, William D. Martin, Anne S. De Groot, Mark C. Poznansky, Ann E. Sluder, Anja Garritsen
bioRxiv 582007; doi: https://doi.org/10.1101/582007
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Coxiella burnetii epitope-specific T-cell responses in chronic Q fever patients
Anja Scholzen, Guilhem Richard, Leonard Moise, Eva Hartman, Chantal P. Bleeker-Rovers, Patrick M. Reeves, Susan Raju Paul, William D. Martin, Anne S. De Groot, Mark C. Poznansky, Ann E. Sluder, Anja Garritsen
bioRxiv 582007; doi: https://doi.org/10.1101/582007

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