Current influenza vaccines predominantly elicit antibody responses that target the viral surface glycoproteins. As these glycoproteins can differ greatly between strains, vaccines are reformulated annually based on the strains predicted to circulate in the upcoming influenza season, and have reduced efficacy when circulating and vaccine strains are mismatched. Hence, there is great interest in strategies to elicit more cross-strain protective immune responses.
Unlike antibodies, CD8+ T cells target and eliminate infected cells via recognition of viral peptides presented by Human Leukocyte Antigen class I molecules (HLA-I) at the cell surface. These peptides are derived from the proteasomal breakdown of proteins within the cell, thus encompass peptides from more conserved internal viral components. This makes the HLA-I-CD8+ T cell axis attractive for generation of cross-strain protective immunity. We have developed a mass spectrometry-based epitope discovery workflow for identification of influenza peptides naturally presented by HLA-I of infected cells. We are currently applying this workflow to common HLA-I variants present in the human population and are developing an epitope conservation and mapping platform to define regions of influenza virus with capacity to elicit cross-strain protective immunity. Such understanding will aid rational design of influenza vaccines for T cell-mediated cross-strain protection across the human population.