Format

Send to

Choose Destination
Infect Immun. 2019 Sep 19;87(10). pii: e00213-19. doi: 10.1128/IAI.00213-19. Print 2019 Oct.

Coxiella burnetii Epitope-Specific T-Cell Responses in Patients with Chronic Q Fever.

Author information

1
InnatOss Laboratories B.V., Oss, the Netherlands.
2
EpiVax, Inc., Providence, Rhode Island, USA.
3
Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, Rhode Island, USA.
4
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
5
Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
6
Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, Massachusetts, USA asluder@mgh.harvard.edu anja.garritsen@innatoss.com.
7
InnatOss Laboratories B.V., Oss, the Netherlands asluder@mgh.harvard.edu anja.garritsen@innatoss.com.
#
Contributed equally

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. In this study, we investigated in a cohort of 22 individuals treated for 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. In cultured enzyme-linked immunosorbent spot (ELISpot) assays, individuals with chronic Q fever showed strong class II epitope-specific responses that were 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 nonreactive in subjects with chronic Q fever. Consistent with more recent/prolonged exposure, we found, however, stronger ex vivo responses by direct ELISpot to both whole-cell C. burnetii and individual peptides in chronic patients than in convalescents. In conclusion, we have validated and expanded a previously published set of candidate epitopes for a novel T-cell targeted subunit Q fever vaccine in treated patients with chronic Q fever and demonstrated that they successfully mounted a T-cell response comparable to that of convalescents. Finally, we demonstrated 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.

KEYWORDS:

Coxiella ; ELISpot; Q fever; T cell; chronic; epitope; infection; peptide

PMID:
31331958
PMCID:
PMC6759312
[Available on 2020-03-19]
DOI:
10.1128/IAI.00213-19
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center