Modified influenza M158-66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge

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

doi:10.1038/s41541-023-00705-y

Modified influenza M1_58-66 peptide vaccination induces non-relevant T-cells and may enhance pathology after challenge

NPJ Vaccines. 2023 Aug 12;8(1):116. doi: 10.1038/s41541-023-00705-y.

Authors

Affiliations

¹ Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
² Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
³ Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.
⁴ Microscope Consultancy, Weesp, Netherlands.
⁵ Virology & Immunology Research. Dept Medical Microbiology and Infection prevention, University Medical Center Groningen, Groningen, the Netherlands.
⁶ Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands. Jorgen.de.jonge@rivm.nl.

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 M1_58-66 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.