Towards Future T Cell-Mediated Influenza Vaccines

Influenza A virus infections (IAVs) impact significantly on global health, being particularly problematic in children, the elderly, pregnant women, indigenous populations and people with co-morbidities. Antibody-based vaccines require annual administration to combat rapidly acquired mutations modifying the surface haemagglutinin (HA) and neuraminidase (NA) glycoproteins. Conversely, influenza-specific CD8 T cell responses directed at peptides derived from the more conserved internal virus proteins are known to be protective, suggesting that T cell-based vaccines may provide long-lasting cross-protection. This review outlines the importance of CD8 T cell immunity to seasonal influenza and pandemic IAVs and summarises current vaccination strategies for inducing durable CD8 T cell memory. Aspectsof future IAV vaccine design and the useof live virus challenge in humans to establish proof of principle are also discussed.