Influenza viruses are a significant cause of respiratory illnesses, inflicting a high level of morbidity and mortality worldwide especially in at risk populations such as the young and elderly. Current vaccines are formulated based on the strains predicted to circulate in the upcoming season and induce predominantly antibody-based immune responses against the surface glycoproteins. Due to antigenic drift and shift, these glycoproteins can differ greatly between strains resulting in limited cross-strain protection. In contrast, CD8+ T cells can recognise virus-derived peptides displayed by HLA class I molecules (HLA-I) on the surface of infected cells. These peptides are generated through the breakdown of viral proteins within the cell, hence include peptides derived from more conserved internal viral proteins, building capacity for T cell responses that target a range of strains.
To determine which viral components have the potential to stimulate CD8+ T cell responses, we have developed a mass spectrometry-based epitope discovery approach, isolating peptides from the HLA-I of infected cells to determine the naturally presented virus-derived peptides available for immune surveillance. Utilising a de novo assisted database searching strategy (PEAKS 8.5, BSI), combined with in-house software, we have mapped the contribution of both genome templated (linear) and a newly recognised subset of non-genome templated (spliced) peptides to the array of peptides displayed by the HLA-I. Current work moves to assess the contribution of both linear and spliced peptide subsets to the anti-influenza immune response in healthy donors. The knowledge of which viral components can instigate immune responses is fundamental to the rational design of vaccines to maximise T cell responses, hence these data will help inform future strategies for the generation of a universal influenza vaccine. This work is funded by the Human Vaccines Project Michelson Prizes for Human Immunology and Vaccine Research.