Prospects for an influenza vaccine that induces cross-protective cytotoxic T lymphocytes

Our approach to vaccination against influenza is unique. For no other pathogen do we construct and produce a new vaccine every year in the face of uncertainty about the strains that will be circulating when it is used. The huge global cooperative effort that underpins this process reflects our awareness of the need to control this major pathogen. Moreover, the threat of devastation by a pandemic due to a newly emerging viral subtype has triggered an intense effort to improve and accelerate the production of vaccines for use if a pandemic arises. However, type A influenza viruses responsible for seasonal epidemics and those with the potential to cause a pandemic share amino acid sequences that form the targets of cytotoxic T lymphocytes (CTL). CTL activated by currently circulating viruses, therefore, offer a possible means to limit the impact of infection with future variant seasonal strains and even new subtypes. This review examines how cross-protective CTL can be exploited to improve influenza vaccination and issues that need to be considered when attempting to induce this type of immunity. We discuss the role of CTL responses in viral control and review the current knowledge relating to specificity and longevity of memory CD8(+) T cells, how vaccine antigen can be loaded into antigen-presenting cells to prime these responses and factors influencing the class of response induced. Application of these principles to the next generation of influenza vaccines should lead to much greater control of infection.