Influenza Vaccination: Accelerating the Process for New Vaccine Development in Older Adults.

Increased susceptibility to the serious complications of influenza is common in older adults. It is often ascribed to weakening of the immune system with age, and 90% of influenza-related deaths occur in older adults despite widespread vaccination programs. Common chronic conditions not only contribute to the loss of immune protection after vaccination and increase the risk for serious outcomes of influenza, but also increase the long-term consequences following hospitalization. Interactions of T and B cell ageing, chronic elevation of inflammatory cytokines (sometimes dubbed "inflammaging"), and dysregulated acute cytokine production pose major challenges to the development of new and more effective vaccines. However, these age-related problems are modifiable, as we have shown, and provide a clear margin for improvement. This chapter describes how an exclusive focus on developing influenza vaccines to stimulate strain-specific antibody responses against the hemagglutinin surface glycoprotein of the influenza virus, to the exclusion of other potentially important mechanisms, is missing the mark in terms of preventing the serious complications of influenza in older adults. Novel approaches are needed to enhance antibody-mediated protection against infection and stimulate cell-mediated immune responses to clear influenza virus from the lungs. These strategies for improving vaccine effectiveness will address the public health need for "vaccine prevention of disability" to mitigate the global pressures of aging populations on health and social care systems.