Evaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunity
T cell-mediated immunity plays a central role in the control and clearance of intracellular Coxiella burnetii infection, which can cause Q fever. Therefore, we aimed to develop a novel T cell-targeted vaccine that induces pathogen-specific cell-mediated immunity to protect against Q fever in humans...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Frontiers Media
2022
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| _version_ | 1797107407750430720 |
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| author | Sluder, AE Raju Paul, S Moise, L Dold, C Richard, G Silva-Reyes, L Baeten, LA Scholzen, A Reeves, PM Pollard, AJ Garritsen, A Bowen, RA De Groot, AS Rollier, C Poznansky, MC |
| author_facet | Sluder, AE Raju Paul, S Moise, L Dold, C Richard, G Silva-Reyes, L Baeten, LA Scholzen, A Reeves, PM Pollard, AJ Garritsen, A Bowen, RA De Groot, AS Rollier, C Poznansky, MC |
| author_sort | Sluder, AE |
| collection | OXFORD |
| description | T cell-mediated immunity plays a central role in the control and clearance of intracellular Coxiella burnetii infection, which can cause Q fever. Therefore, we aimed to develop a novel T cell-targeted vaccine that induces pathogen-specific cell-mediated immunity to protect against Q fever in humans while avoiding the reactogenicity of the current inactivated whole cell vaccine. Human HLA class II T cell epitopes from C. burnetii were previously identified and selected by immunoinformatic predictions of HLA binding, conservation in multiple C. burnetii isolates, and low potential for cross-reactivity with the human proteome or microbiome. Epitopes were selected for vaccine inclusion based on long-lived human T cell recall responses to corresponding peptides in individuals that had been naturally exposed to the bacterium during a 2007-2010 Q fever outbreak in the Netherlands. Multiple viral vector-based candidate vaccines were generated that express concatemers of selected epitope sequences arranged to minimize potential junctional neo-epitopes. The vaccine candidates caused no antigen-specific reactogenicity in a sensitized guinea pig model. A subset of the vaccine epitope peptides elicited antigenic recall responses in splenocytes from C57BL/6 mice previously infected with C. burnetii. However, immunogenicity of the vaccine candidates in C57BL/6 mice was dominated by a single epitope and this was insufficient to confer protection against an infection challenge, highlighting the limitations of assessing human-targeted vaccine candidates in murine models. The viral vector-based vaccine candidates induced antigen-specific T cell responses to a broader array of epitopes in cynomolgus macaques, establishing a foundation for future vaccine efficacy studies in this large animal model of C. burnetii infection. |
| first_indexed | 2024-03-07T07:15:37Z |
| format | Journal article |
| id | oxford-uuid:9eb7a36a-2854-4d9f-a732-9f9269792e91 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:15:37Z |
| publishDate | 2022 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:9eb7a36a-2854-4d9f-a732-9f9269792e912022-07-29T14:56:21ZEvaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9eb7a36a-2854-4d9f-a732-9f9269792e91EnglishSymplectic ElementsFrontiers Media2022Sluder, AERaju Paul, SMoise, LDold, CRichard, GSilva-Reyes, LBaeten, LAScholzen, AReeves, PMPollard, AJGarritsen, ABowen, RADe Groot, ASRollier, CPoznansky, MCT cell-mediated immunity plays a central role in the control and clearance of intracellular Coxiella burnetii infection, which can cause Q fever. Therefore, we aimed to develop a novel T cell-targeted vaccine that induces pathogen-specific cell-mediated immunity to protect against Q fever in humans while avoiding the reactogenicity of the current inactivated whole cell vaccine. Human HLA class II T cell epitopes from C. burnetii were previously identified and selected by immunoinformatic predictions of HLA binding, conservation in multiple C. burnetii isolates, and low potential for cross-reactivity with the human proteome or microbiome. Epitopes were selected for vaccine inclusion based on long-lived human T cell recall responses to corresponding peptides in individuals that had been naturally exposed to the bacterium during a 2007-2010 Q fever outbreak in the Netherlands. Multiple viral vector-based candidate vaccines were generated that express concatemers of selected epitope sequences arranged to minimize potential junctional neo-epitopes. The vaccine candidates caused no antigen-specific reactogenicity in a sensitized guinea pig model. A subset of the vaccine epitope peptides elicited antigenic recall responses in splenocytes from C57BL/6 mice previously infected with C. burnetii. However, immunogenicity of the vaccine candidates in C57BL/6 mice was dominated by a single epitope and this was insufficient to confer protection against an infection challenge, highlighting the limitations of assessing human-targeted vaccine candidates in murine models. The viral vector-based vaccine candidates induced antigen-specific T cell responses to a broader array of epitopes in cynomolgus macaques, establishing a foundation for future vaccine efficacy studies in this large animal model of C. burnetii infection. |
| spellingShingle | Sluder, AE Raju Paul, S Moise, L Dold, C Richard, G Silva-Reyes, L Baeten, LA Scholzen, A Reeves, PM Pollard, AJ Garritsen, A Bowen, RA De Groot, AS Rollier, C Poznansky, MC Evaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunity |
| title | Evaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunity |
| title_full | Evaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunity |
| title_fullStr | Evaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunity |
| title_full_unstemmed | Evaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunity |
| title_short | Evaluation of a human T cell-targed multi-epitope vaccine for Q fever in animal models of Coxiella burnetii immunity |
| title_sort | evaluation of a human t cell targed multi epitope vaccine for q fever in animal models of coxiella burnetii immunity |
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