Identification of protective and non-protective T cell epitopes in influenza

Understanding the immune response to different CD8 T cell epitopes is important for the development of vaccines designed to promote protective cellular immunity. Recently, we have shown that vaccination with the PA224–233/Db epitope of influenza virus was poorly protective in terms of viral clearance. To determine if other influenza virus epitopes behave in this manner, we analyzed the ability of three newly identified CD8 T cell epitopes and three previously defined epitopes to provide protection following vaccination and viral challenge. All six of the peptide-based vaccinations resulted in significantly increased numbers of epitope-specific CD8 T cells in the spleen. Interestingly, we found that vaccination with three peptides (HA332–340, M1128–135, or PA224–233) resulted in delayed viral clearance following infection. These findings indicate that some epitopes have a detrimental impact on viral clearance and have important implications for the development of vaccination strategies designed to provide protection against subsequent influenza virus challenge.