Modified influenza M158-66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge
Lanfermeijer, Josien van de Ven, Koen van Dijken, Harry Hendriks, Marion Talavera Ormeño, Cami MP de Heij, Femke Roholl, Paul Borghans, José AM van Baarle, Debbie de Jonge, Jørgen
Lanfermeijer, Josien
van de Ven, Koen
van Dijken, Harry
Hendriks, Marion
Talavera Ormeño, Cami MP
de Heij, Femke
Roholl, Paul
Borghans, José AM
van Baarle, Debbie
de Jonge, Jørgen
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Open Access
Type
Article
Language
en
Date of publication
2023-08-12
Year of publication
Research Projects
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Journal Issue
Title
Modified influenza M158-66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge
Translated Title
Published in
NPJ Vaccines 2023; 8(1):116
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.