Modified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge
Abstract CD8 + T cells are promising targets for vaccination against influenza A virus (IAV) infection. Their induction via peptide vaccination is not trivial, because peptides are weakly immunogenic. One strategy to overcome this is by vaccination with chemically enhanced altered peptide ligands (C...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00705-y |
| _version_ | 1827724882240077824 |
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| author | Josien Lanfermeijer Koen van de Ven Harry van Dijken Marion Hendriks Cami M. P. Talavera Ormeño Femke de Heij Paul Roholl José A. M. Borghans Debbie van Baarle Jørgen de Jonge |
| author_facet | Josien Lanfermeijer Koen van de Ven Harry van Dijken Marion Hendriks Cami M. P. Talavera Ormeño Femke de Heij Paul Roholl José A. M. Borghans Debbie van Baarle Jørgen de Jonge |
| author_sort | Josien Lanfermeijer |
| collection | DOAJ |
| description | Abstract CD8 + T cells are promising targets for vaccination against influenza A virus (IAV) infection. Their induction via peptide vaccination is not trivial, because peptides are weakly immunogenic. One strategy to overcome this is by vaccination with chemically enhanced altered peptide ligands (CPLs), which have improved MHC-binding and immunogenicity. It remains unknown how peptide-modification affects the resulting immune response. We studied the effect of CPLs derived from the influenza M158–66 epitope (GILGFVFTL) on the T-cell response. In HLA-A2*0201 transgenic mice, CPL-vaccination led to higher T-cell frequencies, but only a small percentage of the induced T cells recognized the GILG-wildtype (WT) peptide. CPL-vaccination resulted in a lower richness of the GILG-WT-specific T-cell repertoire and no improved protection against IAV-infection compared to GILG-WT peptide-vaccination. One CPL even appeared to enhance pathology after IAV-challenge. CPL-vaccination thus induces T cells not targeting the original peptide, which may lead to potential unwanted side effects. |
| first_indexed | 2024-03-10T22:20:44Z |
| format | Article |
| id | doaj.art-dcf333a662a7405bb9eb73687aa9e066 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-10T22:20:44Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-dcf333a662a7405bb9eb73687aa9e0662023-11-19T12:17:53ZengNature Portfolionpj Vaccines2059-01052023-08-018111410.1038/s41541-023-00705-yModified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challengeJosien Lanfermeijer0Koen van de Ven1Harry van Dijken2Marion Hendriks3Cami M. P. Talavera Ormeño4Femke de Heij5Paul Roholl6José A. M. Borghans7Debbie van Baarle8Jørgen de Jonge9Center for Infectious Disease Control, National Institute for Public Health and the EnvironmentCenter for Infectious Disease Control, National Institute for Public Health and the EnvironmentCenter for Infectious Disease Control, National Institute for Public Health and the EnvironmentCenter for Infectious Disease Control, National Institute for Public Health and the EnvironmentDepartment of Cell and Chemical Biology, Leiden University Medical CentreCenter for Infectious Disease Control, National Institute for Public Health and the EnvironmentMicroscope ConsultancyCenter for Translational Immunology, University Medical Center UtrechtCenter for Infectious Disease Control, National Institute for Public Health and the EnvironmentCenter for Infectious Disease Control, National Institute for Public Health and the EnvironmentAbstract CD8 + T cells are promising targets for vaccination against influenza A virus (IAV) infection. Their induction via peptide vaccination is not trivial, because peptides are weakly immunogenic. One strategy to overcome this is by vaccination with chemically enhanced altered peptide ligands (CPLs), which have improved MHC-binding and immunogenicity. It remains unknown how peptide-modification affects the resulting immune response. We studied the effect of CPLs derived from the influenza M158–66 epitope (GILGFVFTL) on the T-cell response. In HLA-A2*0201 transgenic mice, CPL-vaccination led to higher T-cell frequencies, but only a small percentage of the induced T cells recognized the GILG-wildtype (WT) peptide. CPL-vaccination resulted in a lower richness of the GILG-WT-specific T-cell repertoire and no improved protection against IAV-infection compared to GILG-WT peptide-vaccination. One CPL even appeared to enhance pathology after IAV-challenge. CPL-vaccination thus induces T cells not targeting the original peptide, which may lead to potential unwanted side effects.https://doi.org/10.1038/s41541-023-00705-y |
| spellingShingle | Josien Lanfermeijer Koen van de Ven Harry van Dijken Marion Hendriks Cami M. P. Talavera Ormeño Femke de Heij Paul Roholl José A. M. Borghans Debbie van Baarle Jørgen de Jonge Modified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge npj Vaccines |
| title | Modified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge |
| title_full | Modified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge |
| title_fullStr | Modified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge |
| title_full_unstemmed | Modified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge |
| title_short | Modified influenza M158–66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge |
| title_sort | modified influenza m158 66 peptide vaccination induces non relevant t cells and may enhance pathology after challenge |
| url | https://doi.org/10.1038/s41541-023-00705-y |
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