Development of an adjuvanted, higher-dose, cell-based influenza vaccine: combining advanced technologies to improve vaccine effectiveness.

INTRODUCTION: Influenza remains a significant public health burden, particularly for high-risk populations such as older adults and those with chronic diseases. Effectiveness of standard-dose egg-grown influenza vaccines in these populations is variable and often adversely affected by antigenic drift and/or antigenic mismatch due to egg adaptation during manufacturing. In high-risk groups, vaccine effectiveness may be further reduced by immunosenescence and inflammation. Even modest improvements to seasonal influenza vaccine effectiveness could have a substantial public health benefit. AREAS COVERED: Three key innovations already in widespread use have improved the effectiveness of influenza vaccines. First, vaccine adjuvants such as MF59 increase the magnitude, breadth, and duration of immune responses to both homologous and heterologous strains. Second, higher antigen doses boost immunogenicity and effectiveness. Third, propagation of vaccine strains in cell culture rather than embryonated hens' eggs avoids egg-adaptive mutations that can alter the antigenicity of the vaccine virus. EXPERT OPINION: The individual benefits of each of these innovations inform the rationale for the development of a vaccine that combines them to further leverage their benefits: an adjuvanted, higher-dose, trivalent cell-based influenza vaccine (aTIVc). Early studies on aTIVc show that it elicits strong immune responses with an acceptable reactogenicity profile.